Search results for: brain stimulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1510

Search results for: brain stimulation

820 Structural Correlates of Reduced Malicious Pleasure in Huntington's Disease

Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

Abstract:

Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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819 Joubert Syndrome and Related Disorders: A Single Center Experience

Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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818 An Inquiry on Imaging of Soft Tissues in Micro-Computed Tomography

Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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817 Development and Clinical Application of a Cochlear Implant Mapping Assistance System

Authors: Hong Mengdi, Li Jianan, Ji Fei, Chen Aiting, Wang Qian

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Objective: To overcome the communication barriers that audiologists encounter during cochlear implant mapping, particularly the challenge of eliciting subjective feedback from recipients regarding electrical stimulation, and to enhance the capabilities of existing technologies, we teamed up with software engineers to design an interactive approach for patient-audiologist communication. This approach employs a tablet (PAD) as the interface for a communication and feedback system between patients and audiologists during the mapping process, known as the Cochlear Implant Mapping Assistance System. Methods: Capitalizing on the touchscreen functionality of the PAD, the recipients' subjective feedback during cochlear implant mapping is instantly transmitted to the audiologist's mapping computer. The system acts as a platform for auditory assessment instruments, facilitating immediate evaluation of recipients' post-mapping hearing and speech discrimination capabilities. Furthermore, the system is designed to augment the visual reinforcement audiometry (VRA) process. The system consists of six modules, including three testing projects: loudness testing, hearing threshold testing, and loudness balance testing; two assessment projects: warble tone testing and digit speech testing; and one VRA animation project. It also incorporates speech-to-text and text input display functions tailored to accommodate speech communication difficulties in hearing-impaired individuals, with pre-installed common exchange content between audiologists and recipients. Audiologists can input sentences by selecting options. The system supports switching between Chinese and English versions, suitable for audiologists and recipients who use English, facilitating international application of the system. Results: The Cochlear Implant Mapping Assistance System has been in use for over a year in the Auditory Implant Center of the Department of Otology and Neurotology, Medical Center of Otology and Head & Neck Surgery, Chinese PLA General Hospital, with more than 300 recipients using this mapping system. Currently, the system operates stably, with both audiologists and recipients providing positive feedback, indicating a significant improvement over previous methods. It is particularly well-received by pediatric recipients, significantly enhancing the work efficiency of audiologists and improving the feedback efficiency and accuracy of recipients. The system enhances the comprehensibility for cochlear implant recipients, improves wearing comfort and user experience, facilitates cochlear implant auditory mapping, and increases the collection of previously challenging-to-obtain data during the existing assisted mapping process, such as loudness testing data, electrical stimulation testing data, warble tone testing data, loudness balance testing data, digit speech testing data, and visual reinforcement audiometry testing data. Real-time data recording improves the accuracy of assisted mapping. The interface design is meticulously crafted to accommodate patients of varying ages and cognitive abilities, featuring an intuitive design that allows for effortless, guidance-free use by patients.

Keywords: audiologist, subjective feedback, mapping, cochlear implant

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816 Coronin 1C and miR-128A as Potential Diagnostic Biomarkers for Glioblastoma Multiform

Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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815 Contraction and Membrane Potential of C2C12 with GTXs

Authors: Bayan Almofty, Yuto Yamaki, Tadamasa Terai, Sadahito Uto

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Culture techniques of skeletal muscle cells are advanced in the field of regenerative medicine and applied research of cultured muscle. As applied research of cultured muscle, myopathy (muscles disease) treatment is expected and development bio of actuator is also expected in biomedical engineering. Grayanotoxins (GTXs) is known as neurotoxins that enhance the permeability of cell membrane for Na ions. Grayanotoxins are extracted from a famous Pieris japonica and Ericaceae as well as a phytotoxin. In this study, we investigated the effect of GTXs on muscle cells (C2C12) contraction and membrane potential. Contraction of myotubes is induced by applied external electrical stimulation. Contraction and membrane potential change of skeletal muscle cells are induced by injection of current. We, therefore, concluded that effect of Grayanotoxins on contraction and membrane potential of C2C12 relate to acute toxicity of GTXs.

Keywords: skeletal muscle cells C2C12, grayanotoxins, contraction, membrane potential, acute toxicity, pytotoxin, motubes

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814 ECOSURF EH3 - A Taq DNA Polymerase Enhancer

Authors: Kimberley Phoena Fan, Yu Zhang

Abstract:

ECOSURF™ EH-3 Surfactant (EH3) is a nonionic surfactant and has superior wetting and excellent oil removal properties. It is biodegradable with low toxicity and meets or exceeds US EPA Design for the Environment Criteria, and is widely used as a home cleaner, commercial and industrial degreaser. We have recently found that EH3 also possesses a special function which is characterized as an enhancer to Taq DNA polymerase and ameliorator to reduce the effects of PCR inhibitors, i.e., blood, urea, Guanidinium thiocyanate, Humic acids, polyphenol, and Polysaccharides. This is a new kind of PCR enhancer that does not work on relieving secondary structures of GC-rich templates. We have compared EH3’s effects on Taq DNA Polymerase along with other well-known enhancers, such as DMSO, betaine, and BSA, using GC rich or deficient template and found that, unlike DMSO and Betaine, the EH3 boosting effect on PCR reaction is not through reducing Tm. The results show the same increase of PCR products regardless of the GC contents or secondary structures. The mechanism of EH3 enhancing PCR is through its direct interaction with or stimulation of the DNA polymerase and making the enzymes more resistant to inhibitors in the presence of EH3. This phenomenon has first been observed for EH3, a new type of PCR enzyme enhancer. Subsequent research also shows that a series of similar surfactants boost Taq DNA polymerase as well.

Keywords: EH3, DNA, polymerase, enhancer, raw biological samples

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813 Optimization of Multi-Zone Unconventional (Shale) Gas Reservoir Using Hydraulic Fracturing Technique

Authors: F. C. Amadi, G. C. Enyi, G. G. Nasr

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Hydraulic fracturing is one of the most important stimulation techniques available to the petroleum engineer to extract hydrocarbons in tight gas sandstones. It allows more oil and gas production in tight reservoirs as compared to conventional means. The main aim of the study is to optimize the hydraulic fracturing as technique and for this purpose three multi-zones layer formation is considered and fractured contemporaneously. The three zones are named as Zone1 (upper zone), Zone2 (middle zone) and Zone3 (lower zone) respectively and they all occur in shale rock. Simulation was performed with Mfrac integrated software which gives a variety of 3D fracture options. This simulation process yielded an average fracture efficiency of 93.8%for the three respective zones and an increase of the average permeability of the rock system. An average fracture length of 909 ft with net height (propped height) of 210 ft (average) was achieved. Optimum fracturing results was also achieved with maximum fracture width of 0.379 inches at an injection rate of 13.01 bpm with 17995 Mscf of gas production.

Keywords: hydraulic fracturing, optimisation, shale, tight reservoir

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812 Altered States of Consciousness in Narrative Cinema: Subjective Film Sound

Authors: Mladen Milicevic

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In this paper, subjective film sound will be addressed as it gets represented in narrative cinema. First, 'meta-diegetic' sound will be briefly explained followed by transition to “oneiric” sound. The representation of oneiric sound refers to a situation where film characters are experiencing some sort of an altered state of consciousness. Looking at an antlered state of consciousness in terms of human brain processes will point out to the cinematic ways of expression, which 'mimic' those processes. Using several examples for different films will illustrate these points.

Keywords: oneiric, ASC, film, sound

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811 Impact of Gold and Silver Nanoparticles on Terrestrial Flora and Microorganisms

Authors: L. Steponavičiūtė, L. Steponavičienė

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Despite the rapid nanotechnology progress and recognition, its potential impact in ecosystems and health of humans is still not fully known. In this paper, the study of ecotoxicological dangers of nanomaterials is presented. By chemical reduction method, silver (AgNPs) and gold (AuNPs) nanoparticles were synthesized, characterized and used in experiments to examine their impact on microorganisms (Escherichia coli, Staphylococcus aureus and Candida albicans) and terrestrial flora (Phaseolus vulgaris and Lepidium sativum). The results collected during experiments with terrestrial flora show tendentious growth stimulations caused by gold nanoparticles. In contrast to these results, silver nanoparticle solutions inhibited growth of beans and garden cress, compared to control samples. The results obtained from experiments with microorganisms show similarities with ones collected from experiments with terrestrial plants. Samples treated with AuNPs of size 13 nm showed stimulation in the growth of the colonies compared with 3,5 nm size nanoparticles.

Keywords: nanomaterials, ecotoxicology, nanoparticles, ecosystems

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810 Effect of Papaverine on Developmental Neurotoxicity: Neurosphere as in vitro Model

Authors: Mohammed Y. Elsherbeny, Mohamed Salama, Ahmed Lotfy, Hossam Fareed, Nora Mohammed

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Background: Developmental neurotoxicity (DNT) entails the toxic effects imparted by various chemicals on brain during the early childhood when human brains are vulnerable during this period. DNT study in vivo cannot determine the effect of the neurotoxins, as it is not applicable, so using the neurosphere cells of lab animals as an alternative is applicable and time saving. Methods: Cell culture: Rat neural progenitor cells were isolated from rat embryos’ brain. The cortices were aseptically dissected out and the tissues were triturated. The dispersed tissues were allowed to settle. The supernatant was then transferred to a fresh tube and centrifuged. The pellet was placed in Hank’s balanced salt solution and cultured as free-floating neurospheres in proliferation medium. Differentiation was initiated by growth factor withdrawal in differentiation medium and plating onto a poly-d-lysine/ laminin matrix. Chemical Exposure: Neurospheres were treated for 2 weeks with papaverine in proliferation medium. Proliferation analyses: Spheres were cultured. After 0, 4, 5, 11 and 14 days, sphere size was determined by software analyses (CellProfiler, version 2.1; Broad Institute). Diameter of each neurosphere was measured and exported to excel file further to statistical analysis. Viability test: Trypsin-EDTA solution was added to neurospheres to dissociate neurospheres into single cells suspension, then viability evaluated by the Trypan Blue exclusion test. Result: As regards proliferation analysis and percentage of viable cells of papaverin treated groups: There was no significant change in cells proliferation compared to control at 0, 4, 5, 11 and 14 days with concentrations 1, 5 and 10 µM of papaverine, but there is a significant change in cell viability compared to control after 1 week and 2 weeks with the same concentrations of papaverine. Conclusion: Papaverine has toxic effect on viability of neural cell, not on their proliferation, so it may produce focal neural lesions not growth morphological changes.

Keywords: developmental neurotoxicity, neurotoxin, papaverine, neuroshperes

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809 Connectomic Correlates of Cerebral Microhemorrhages in Mild Traumatic Brain Injury Victims with Neural and Cognitive Deficits

Authors: Kenneth A. Rostowsky, Alexander S. Maher, Nahian F. Chowdhury, Andrei Irimia

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The clinical significance of cerebral microbleeds (CMBs) due to mild traumatic brain injury (mTBI) remains unclear. Here we use magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and connectomic analysis to investigate the statistical association between mTBI-related CMBs, post-TBI changes to the human connectome and neurological/cognitive deficits. This study was undertaken in agreement with US federal law (45 CFR 46) and was approved by the Institutional Review Board (IRB) of the University of Southern California (USC). Two groups, one consisting of 26 (13 females) mTBI victims and another comprising 26 (13 females) healthy control (HC) volunteers were recruited through IRB-approved procedures. The acute Glasgow Coma Scale (GCS) score was available for each mTBI victim (mean µ = 13.2; standard deviation σ = 0.4). Each HC volunteer was assigned a GCS of 15 to indicate the absence of head trauma at the time of enrollment in our study. Volunteers in the HC and mTBI groups were matched according to their sex and age (HC: µ = 67.2 years, σ = 5.62 years; mTBI: µ = 66.8 years, σ = 5.93 years). MRI [including T1- and T2-weighted volumes, gradient recalled echo (GRE)/susceptibility weighted imaging (SWI)] and gradient echo (GE) DWI volumes were acquired using the same MRI scanner type (Trio TIM, Siemens Corp.). Skull-stripping and eddy current correction were implemented. DWI volumes were processed in TrackVis (http://trackvis.org) and 3D Slicer (http://www.slicer.org). Tensors were fit to DWI data to perform DTI, and tractography streamlines were then reconstructed using deterministic tractography. A voxel classifier was used to identify image features as CMB candidates using Microbleed Anatomic Rating Scale (MARS) guidelines. For each peri-lesional DTI streamline bundle, the null hypothesis was formulated as the statement that there was no neurological or cognitive deficit associated with between-scan differences in the mean FA of DTI streamlines within each bundle. The statistical significance of each hypothesis test was calculated at the α = 0.05 level, subject to the family-wise error rate (FWER) correction for multiple comparisons. Results: In HC volunteers, the along-track analysis failed to identify statistically significant differences in the mean FA of DTI streamline bundles. In the mTBI group, significant differences in the mean FA of peri-lesional streamline bundles were found in 21 out of 26 volunteers. In those volunteers where significant differences had been found, these differences were associated with an average of ~47% of all identified CMBs (σ = 21%). In 12 out of the 21 volunteers exhibiting significant FA changes, cognitive functions (memory acquisition and retrieval, top-down control of attention, planning, judgment, cognitive aspects of decision-making) were found to have deteriorated over the six months following injury (r = -0.32, p < 0.001). Our preliminary results suggest that acute post-TBI CMBs may be associated with cognitive decline in some mTBI patients. Future research should attempt to identify mTBI patients at high risk for cognitive sequelae.

Keywords: traumatic brain injury, magnetic resonance imaging, diffusion tensor imaging, connectomics

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808 Family Satisfaction with Neuro-Linguistic Care for Patients with Alzheimer’s Disease

Authors: Sara Sahraoui

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This research studied the effect of Alzheimer's disease (AD) on language information processing in subjects with Alzheimer’s disease (AD) who were bilingual (French and dialectical Arabic). The results show a disorder of certain semantic aspects of their mother tongue (L1). On the other hand, grammatical levels appeared to be relatively unaffected in oral speech in L1 but were disturbed in the second language (L2). In consequence, we constructed a cognitive-language stimulation protocol for bilingual patients (PSCLAB) to respond to this disorder. The efficacy of this protocol in terms of rehabilitation was assessed in 30 such patients through discourse analysis carried out before and after initiating the protocol. The results show that cognitive/language training using the PSCLAB appears to improve the language behaviour of bilingual patients with AD. However, this survey study aims to verify the satisfaction of patients’ relatives with the results of cognitive language training by PSCLAB. We developed a brief instrument to measure the satisfaction of family members. The results report that the patient's relatives are satisfied with the results of cognitive training by PSCLAB.

Keywords: satisfaction, Alzheimer's disease, rehabilitation, levels language

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807 Musical Education of Preschool Children: From the Average to the Gifted

Authors: Eudjen Cinc

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The contemporary society, which is, whether we like it or not, oriented towards utilitarianism, pragmatics and professional flexibility, lives in a certain paradox. On the one hand, at least declaratively, the accent of modern society is on knowledge; knowledge is even considered to be a commodity, the popularity of education is increased as the only means of survival in the market-oriented world, while on the other hand modern society is moving towards simplification and decreasing the amount of information and areas which are considered necessary in the generally excepted concept of education. We cannot talk about the preschool teacher profession without mentioning work with gifted children. The preschool teacher knowing the characteristics of gifted children is of utmost importance because their early identification and professional guidance are of cardinal importance for the direction in which the children will develop. When we talk about musical ability, in the first phase, the role of preschool teachers in the identification and stimulation of gifted children naturally refers to monitoring children’s musical manifestation. The identification process and work with the gifted presupposes a good relationship with the family, synergy of these two important influences in the child’s education and upbringing.

Keywords: music education, gifted children, methodology, kindergarten

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806 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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805 Investigation of the Perceptional Quality of Nightscape in the Urban Space: A Case Study of Mashhad Koohsangi Axis in Iran

Authors: Fahimeh Khatami, Maryam Ziyaee, Elham Sanagar Darbani

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Variety of different factors could influence on the measure urban perception. Both physical and non-physical factors, at least, make the quality of perception through the urban spaces. The value of lighting is one of the important factors which could make the better quality of environmental perception for the user. The perception of urban space in most of the Iranian cities is offer by different factors during the night time which caused to the death of nightlife and social activities. Therefore, this research is an attempt to study on the different of user perception during day and night in the Koohsangi Street. As the case study area in Iran in order to bring out the main influential factors during perception process. To deal with this good we used chi-square test on a sample size made up of on hundred participants. The result shows that for improving the night quality of urban spaces the legibility, navigation, and role stimulation were in important perception factors. Therefore, by focusing on these factors it would be possible to find out more functional solution for improving the activity of night perception.

Keywords: perception, urban space, legibility, imageability, nightscape

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804 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models

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

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

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

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803 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study

Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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802 Multi-omics Integrative Analysis with Genome-Scale Metabolic Model Simulation Reveals Reaction Essentiality data in Human Astrocytes Under the Lipotoxic Effect of Palmitic Acid

Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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801 The Functional Magnetic Resonance Imaging and the Consumer Behaviour: Reviewing Recent Research

Authors: Mikel Alonso López

Abstract:

In the first decade of the twenty-first century, advanced imaging techniques began to be applied for neuroscience research. The Functional Magnetic Resonance Imaging (fMRI) is one of the most important and most used research techniques for the investigation of emotions, because of its ease to observe the brain areas that oxygenate when performing certain tasks. In this research, we make a review about the main research carried out on the influence of the emotions in the decision-making process that is exposed by using the fMRI.

Keywords: decision making, emotions, fMRI, consumer behaviour

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800 Concepts of Instrumentation Scheme for Thought Transfer

Authors: Rai Sachindra Prasad

Abstract:

Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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799 Rapid and Sensitive Detection: Biosensors as an Innovative Analytical Tools

Authors: Sylwia Baluta, Joanna Cabaj, Karol Malecha

Abstract:

The evolution of biosensors was driven by the need for faster and more versatile analytical methods for application in important areas including clinical, diagnostics, food analysis or environmental monitoring, with minimum sample pretreatment. Rapid and sensitive neurotransmitters detection is extremely important in modern medicine. These compounds mainly occur in the brain and central nervous system of mammals. Any changes in the neurotransmitters concentration may lead to many diseases, such as Parkinson’s or schizophrenia. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements.

Keywords: adrenaline, biosensor, dopamine, laccase, tyrosinase

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798 Creativity in Educational Realities: Theoretical Considerations

Authors: Cristina Costa-Lobo, Ana Campina, José Menezes

Abstract:

Creativity implies originality, but originality does not imply the existence of creativity. Today, one of the challenges of the educational context is the development of educated, autonomous, prudent and competent citizens with a critical attitude, a well-founded questioning and a creative search for innovative alternatives and solutions. These supposedly cognitive capacities impose emotional analysis and decision making, and emotion is also considered as a creative act. Authors emphasize the importance of family and school in the creative manifestation of children and young people, and these agents can stimulate or impede creative expression. Thus, children entering the school system are faced with a barrier that blocks the externalization of this competence. This work deals with the implementation of specific strategies and promoters of an educational environment suitable for the development of creativity. The construct of creativity is discussed in a transdisciplinary perspective, and the importance of the construct is enhanced in psychoeducational practices, in challenging and multifaceted environments. It is assumed that the stimulation and early experience of creative thinking in an educational context are conditions that promote the development of problem-solving skills and future challenges.

Keywords: creativity, education, psychology, pedagogy

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797 Subjective Evaluation of Mathematical Morphology Edge Detection on Computed Tomography (CT) Images

Authors: Emhimed Saffor

Abstract:

In this paper, the problem of edge detection in digital images is considered. Three methods of edge detection based on mathematical morphology algorithm were applied on two sets (Brain and Chest) CT images. 3x3 filter for first method, 5x5 filter for second method and 7x7 filter for third method under MATLAB programming environment. The results of the above-mentioned methods are subjectively evaluated. The results show these methods are more efficient and satiable for medical images, and they can be used for different other applications.

Keywords: CT images, Matlab, medical images, edge detection

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796 Effects of Breed and Number of Embryos Transferred on the Efficacy of MOET in Sheep

Authors: Ayman A. Swelum, Abdullah N. Al-Owaimer, Mohamed A. Abouheif

Abstract:

This study aimed to evaluate the effects of sheep breed and the number of embryos transferred on the success of multiple ovulation and embryo transfer (MOET). Sixteen Najdi and Naeimi ewes were used as donors. Multiple ovulation was achieved using equine chorionic gonadotropin (eCG). Thirty-five recipient ewes were divided into four groups: Najdi or Naeimi ewes that received either one or two embryos. After lambing, the gestation length, litter size, and sex of the lambs were recorded. The rates of pregnancy, lambing, and embryo survival were lower in the recipient Najdi than Naeimi ewes when two embryos were transferred. In contrast, the Naeimi ewes that received one embryo had a significantly lower embryo transfer success. In conclusion, the response of ewes to multiple ovulation stimulation using eCG was significantly high in Naeimi ewes (9.8±1.17). Moreover, transferring one embryo resulted in a significantly high pregnancy rate in the Najdi sheep (60%).

Keywords: embryo transfer, multiple ovulation, Najdi, Naeimi, sheep

Procedia PDF Downloads 730
795 Association between Attention Deficit Hyperactivity Disorder Medication, Cannabis, and Nicotine Use, Mental Distress, and Other Psychoactive Substances

Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

Abstract:

Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

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794 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity

Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

Procedia PDF Downloads 99
793 Exploring the Neural Mechanisms of Communication and Cooperation in Children and Adults

Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer

Abstract:

This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.

Keywords: communication, cooperation, development, interaction, neuroscience

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792 Developing Cucurbitacin a Minimum Inhibition Concentration of Meloidogyne Incognita Using a Computer-Based Model

Authors: Zakheleni P. Dube, Phatu W. Mashela

Abstract:

Minimum inhibition concentration (MIC) is the lowest concentration of a chemical that brings about significant inhibition of target organism. The conventional method for establishing the MIC for phytonematicides is tedious. The objective of this study was to use the Curve-fitting Allelochemical Response Data (CARD) to determine the MIC for pure cucurbitacin A on Meloidogyne incognita second-stage juveniles (J2) hatch, immobility and mortality. Meloidogyne incognita eggs and freshly hatched J2 were separately exposed to a series of pure cucurbitacin A concentrations of 0.00, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.25 and 2.50 μg.mL⁻¹for 12, 24, 48 and 72 h in an incubator set at 25 ± 2°C. Meloidogyne incognita J2 hatch, immobility and mortality counts were determined using a stereomicroscope and the significant means were subjected to the CARD model. The model exhibited density-dependent growth (DDG) patterns of J2 hatch, immobility and mortality to increasing concentrations of cucurbitacin A. The average MIC for cucurbitacin A on M. incognita J2 hatch, immobility and mortality were 2.2, 0.58 and 0.63 µg.mL⁻¹, respectively. Meloidogyne incognita J2 hatch had the highest average MIC value followed by mortality and immobility had the least. In conclusion, the CARD model was able to generate MIC for cucurbitacin A, hence it could serve as a valuable tool in the chemical-nematode bioassay studies.

Keywords: inhibition concentration, phytonematicide, sensitivity index, threshold stimulation, triterpenoids.

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791 Exploring Psychosocial Stressors in Crack Cocaine Use

Authors: Yaa Asuaba Duopah, Lisa Moran, Khalifa Elmusharaf, Dervla Kelly

Abstract:

Background: Research has identified a strong link between stress and drug use behaviours. Also, it has been established that the prolonged use of crack cocaine stimulates emotional, cognitive, neurological, and social changes. This paper examines the psychosocial stressors associated with crack cocaine use. Methodology: The study is qualitative and adopts a critical realist approach. Data was collected through 26 face-to-face, in-depth, semi-structured interviews with people who use crack cocaine. Study participants were recruited through two addiction services using purposive. Participants consisted of 15 males and 11 females between the ages of 24-57 years. Data were analysed using thematic analysis. Results: Cravings, financial hardship, family breakdown, and emotional stimulation were revealed as psychosocial stressors associated with crack cocaine use. Conclusion: Addressing the psychosocial stressors identified in this paper through targeted interventions and supportive policies is crucial for improving the well-being of persons who use crack cocaine. Collaboration between addiction, mental health, and support services is recommended to develop and deliver these interventions.

Keywords: psychological stress, substance misuse disorder, mental health, coping

Procedia PDF Downloads 55