Search results for: brain tumor

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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We describe an innovative method for highly specific detection of miRNAs using a specially modified method of poly(A) adaptor RT-qPCR. We use uniquely designed specific extension sequence, which plays important role in providing an opportunity to affect high specificity of miRNA detection. This method involves two steps of reactions as like previously reported and which are poly(A) tailing and reverse-transcription followed by real-time PCR. Firstly, miRNAs are extended by a poly(A) tailing reaction and then converted into cDNA. Here, we remarkably reduced the reaction time by the application of short length of poly(T) adaptor. Next, cDNA is hybridized to the 3’-end of a specific extension sequence which contains miRNA sequence and results in producing a novel PCR template. Thereafter, the SYBR Green-based RT-qPCR progresses with a universal poly(T) adaptor forward primer and a universal reverse primer. The target miRNA, miR-106b in human brain total RNA, could be detected quantitatively in the range of seven orders of magnitude, which demonstrate that the assay displays a dynamic range of at least 7 logs. In addition, the better specificity of this novel extension-based assay against well known poly(A) tailing method for miRNA detection was confirmed by melt curve analysis of real-time PCR product, clear gel electrophoresis and sequence chromatogram images of amplified DNAs.

Keywords: microRNA(miRNA), specific extension sequence, RT-qPCR, poly(A) tailing assay, reverse transcription

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Authors: Fatemeh Keshavarz

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Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier (BBB) due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. interleukin 32 (IL-32) a proinflammatory cytokine that important player in the activation of the innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, Amphiphysin, SOX1, Zic4, ITPR1, CARP, GAD, Recoverin, Titin, and Ganglioside antigens were measured by indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for Ri antigen, which showed a significant relationship compared to the control group. Autoantibodies were also positive in 2 patients for CV2, in 1 patient for Hu, and in 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibody positivity against several nervous system antigens may be involved in the pathogenesis of schizophrenia.

Keywords: schizophrenia, microglia, autoantibodies, IL-32

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Authors: F. Ece Cetin, H. Nezih Ozdemir, Emre Kumral

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Ischemic stroke of the precuneal cortex (PC) alone is extremely rare. This study aims to evaluate the clinical, neurocognitive, and behavioural characteristics of isolated PC infarcts. We assessed neuropsychological and behavioral findings in 12 patients with isolated PC infarct among 3800 patients with ischemic stroke. To determine the most frequently affected brain locus in patients, we first overlapped the ischemic area of patients with specific cognitive disorders and patients without specific cognitive disorders. Secondly, we compared both overlap maps using the 'subtraction plot' function of MRIcroGL. Patients showed various types of cognitive disorders. All patients experienced more than one category of cognitive disorder, except for two patients with only one cognitive disorder. Lesion topographical analysis showed that damage within the anterior precuneal region might lead to consciousness disorders (25%), self-processing impairment (42%), visuospatial disorders (58%), and lesions in the posterior precuneal region caused episodic and semantic memory impairment (33%). The whole precuneus is involved in at least one body awareness disorder. The cause of the stroke was cardioembolism in 5 patients (42%), large artery disease in 3 (25%), and unknown in 4 (33%). This study showed a wide variety of neuropsychological and behavioural disorders in patients with precuneal infarct. Future studies are needed to achieve a proper definition of the function of the precuneus in relation to the extended cortical areas. Precuneal cortex region infarcts have been found to predict a source of embolism from the large arteries or heart.

Keywords: cognition, pericallosal artery, precuneal cortex, ischemic stroke

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Authors: Manal Alosaimi

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Many rehabilitation strategies exist to aid persons with neurological disorders relearn motor skills through intensive training. Evidence supporting the theory that cortical areas involved in motor execution can be triggered by observing actions performed by others is attributed to the function of the mirror neuron system (MNS) indicates that activation of the MNS is associated with improvements in physical action and motor learning. Therefore, it is important to investigate the relationship between motor training (in this case, playing the drums) and the activation of the MNS. To achieve this, 15 healthy right-handed participants received drum-kit training for 21 weeks, during which time blood oxygen level-dependent (BOLD) signals were monitored in the brain using functional magnetic resonance imaging (fMRI). Participants were required to perform action–observation and action–execution fMRI tasks. The main results are that BOLD signals in classical regions of the MNS such as supramarginal gyri, inferior parietal lobule, and supplementary motor area increase significantly over the training period. Activation of these areas indicates that passive-observation of others performing these same skills may facilitate recovery of persons suffering from neurological disorders, and complement conventional rehabilitation programs that focus on action execution or intense training.

Keywords: fMRI, mirror neuron system, magnetic resonance imaging, neuroplasticity, drumming, learning, music, action observation, action execution

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Authors: Chandra Mukherjee

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The prevalent knowledge of the biological systems is based on the standard scientific perception of natural equilibrium, determination and predictability. Recently, a rethinking of concepts was presented and a new scientific perspective emerged that involves complexity theory with deterministic chaos theory, nonlinear dynamics and theory of fractals. The unpredictability of the chaotic processes probably would change our understanding of diseases and their management. The mathematical definition of chaos is defined by deterministic behavior with irregular patterns that obey mathematical equations which are critically dependent on initial conditions. The chaos theory is the branch of sciences with an interest in nonlinear dynamics, fractals, bifurcations, periodic oscillations and complexity. Recently, the biomedical interest for this scientific field made these mathematical concepts available to medical researchers and practitioners. Any biological network system is considered to have a nominal state, which is recognized as a homeostatic state. In reality, the different physiological systems are not under normal conditions in a stable state of homeostatic balance, but they are in a dynamically stable state with a chaotic behavior and complexity. Biological systems like heart rhythm and brain electrical activity are dynamical systems that can be classified as chaotic systems with sensitive dependence on initial conditions. In biological systems, the state of a disease is characterized by a loss of the complexity and chaotic behavior, and by the presence of pathological periodicity and regulatory behavior. The failure or the collapse of nonlinear dynamics is an indication of disease rather than a characteristic of health.

Keywords: HRV, HRVI, LF, HF, DII

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Authors: Ibraheem Husain, Abul Kalam Najmi, Karishma Chester

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First-in-human (FIH) studies are a critical step in clinical development of any molecule that has shown therapeutic promise in preclinical evaluations, since preclinical research and safety studies into clinical development is a crucial step for successful development of monoclonal antibodies for guidance in pharmaceutical industry for the treatment of human diseases. Therefore, comparison between USFDA and nine pharmacologically guided approaches (PGA) (simple allometry, maximum life span potential, brain weight, rule of exponent (ROE), two species methods and one species methods) were made to determine maximum recommended starting dose (MRSD) for first in human clinical trials using four drugs namely Denosumab, Bevacizumab, Anakinra and Omalizumab. In our study, the predicted pharmacokinetic (pk) parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The study indicated that the clearance and volume of distribution of antibodies can be predicted with reasonable accuracy in human and a good estimate of first human dose can be obtained from the predicted human clearance and volume of distribution. A pictorial method evaluation chart was also developed based on fold errors for simultaneous evaluation of various methods.

Keywords: clinical pharmacology (CPH), clinical research (CRE), clinical trials (CTR), maximum recommended starting dose (MRSD), clearance and volume of distribution

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Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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Authors: Sanjeeb Sutradhar, Archita Patnaik

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Histidine is one of the twenty-two naturally occurring essential amino acids exhibiting two conformations, L-histidine and D-histidine. D-Histidine is biologically inert, while L-histidine is bioactive because of its conversion to neurotransmitter or neuromodulator histamine in both brain as well as central nervous system. The deficiency of L-histidine causes serious diseases like Parkinson’s disease, epilepsy and the failure of normal erythropoiesis development. Gold nanocomposites are attractive materials due to their excellent biocompatibility and are easy to adsorb on the electrode surface. In the present investigation, hydrophobic fullerene-C60 was functionalized with homocysteine via nucleophilic addition reaction to make it hydrophilic and to successively make the nanocomposite with in-situ prepared gold nanoparticles with ascorbic acid as reducing agent. The electronic structure calculations of the AuNPs@Hcys-C60 nanocomposite showed a drastic reduction of HOMO-LUMO gap compared to the corresponding molecules of interest, indicating enhanced electron transportability to the electrode surface. In addition, the electrostatic potential map of the nanocomposite showed the charge was distributed over either end of the nanocomposite, evidencing faster direct electron transfer from nanocomposite to the electrode surface. This nanocomposite showed catalytic activity; the nanocomposite modified glassy carbon electrode showed a tenfold higher kₑt, the electron transfer rate constant than the bare glassy carbon electrode. Significant improvement in its sensing behavior by square wave voltammetry was noted.

Keywords: fullerene-C60, gold nanocomposites, L-Histidine, square wave voltammetry

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Authors: Arthur C. Tsai, Chii-Shyang Kuo, Vincent S. C. Chien, Michelle Liou, Philip E. Cheng

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Meditation enhances mental abilities and it is an antidote to anxiety. However, very little is known about brain mechanisms and cortico-subcortical interactions underlying meditation-induced anxiety relief. In this study, the changes of phase-amplitude coupling (PAC) in which the amplitude of the beta frequency band were modulated in phase with delta rhythm were investigated after eight-week of meditation training. The study hypothesized that through a concentrate but relaxed mental training the delta-beta coupling in the frontal regions is attenuated. The delta-beta coupling analysis was applied to within and between maximally-independent component sources returned from the extended infomax independent components analysis (ICA) algorithm on the continuous EEG data during mediation. A unique meditative concentration task through relaxing body and mind was used with a constant level of moderate mental effort, so as to approach an ‘emptiness’ meditative state. A pre-test/post-test control group design was used in this study. To evaluate cross-frequency phase-amplitude coupling of component sources, the modulation index (MI) with statistics to calculate circular phase statistics were estimated. Our findings reveal that a significant delta-beta decoupling was observed in a set of frontal regions bilaterally. In addition, beta frequency band of prefrontal component were amplitude modulated in phase with the delta rhythm of medial frontal component.

Keywords: phase-amplitude coupling, ICA, meditation, EEG

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Authors: Eman S. Soliman, Sana Hawamdeh, Najmus S. Mahfooz

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Purpose: The purpose of this paper was to examine various components of applied emotional intelligence as demonstrated in the leadership style of Khadijah Bint Khuwaylid in pre and post-Islamic society. Methodology: The research used a qualitative research method, specifically historical and ethnographic techniques. Data collection included both primary and secondary sources. Data from sources were analyzed to document the use of emotional intelligent leadership behaviors throughout Khadijah Bint Khuwaylid leadership experience from 596 A.D. to 621 A.D. Findings: Demonstration of four cornerstones of emotional intelligence which are self-awareness, self-management, social awareness and relationship management. Apply them on khadejah Bint Khuwaylid leadership style reveal that she possess main behavioral competences in the form of emotionally self-aware, self-.confidence, adaptability, empathy and influence. Conclusions: Khadijah Bint Khuwaylid serves as a historical model of effective leadership that included the use of emotional intelligence in her leadership behavior. The inclusion of the effective portion of the brain created a successful leadership style that can be learned by present day and future leadership. The recommendations for future leaders are to include the use of emotionally self-aware and self-confidence, adaptability, empathy and influence as components of leadership. This will then demonstrate in a leadership a basic knowledge and understanding of feelings, the keenness to be emotionally open with others, the ability to prototype beliefs and values, and the use of emotions in future communications, vision and progress.

Keywords: emotional intelligence, leadership, Khadijah Bint Khuwaylid, women

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Authors: Assia Galleze, Abdurrahim Kocyigit, Nacira Cherif, Nidel Benhalilou, Nabila Attal, Chafia Touil Boukkoffa, Rachida Raache

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Introduction and aims: Chemotherapeutic agents used to inhibit cell division and reduce tumor growth, increase reactive oxygen species levels, which contributes to their genotoxicity [1]. The comet assay is an inexpensive and rapid method to detect the damage at cellular levels and has been used in various cancer populations undergoing chemotherapy [2,3]. The present study aim to assess the oxidative stress and the genotoxicity induced by chemotherapy by the determination of plasma malondialdehyde (MDA) level, protein carbonyl (PC) content, superoxide dismutase (SOD) activity and lymphocyte DNA damage in Algerian children with lymphoma. Materials and Methods: For our study, we selected thirty children with lymphoma treated in university hospital of Beni Messous, Algeria, and fifty unrelated subjects as controls, after obtaining the informed consent in accordance with the Declaration of Helsinki (1964). Plasma levels of MDA, PC and SOD activity were spectrophotometrically measured, while DNA damage was assessed by alkaline comet assay in peripheral blood leukocytes. Results and Discussion: Plasma MDA, PC levels and lymphocyte DNA damage, were found to be significantly higher in lymphoma patients than in controls (p < 0.001). Whereas, SOD activity in lymphoma patients was significantly lower than in healthy controls (p < 0.001). There were significant positive correlations between DNA damage, MDA and PC in patients (r = 0.96, p < 0.001, r = 0.97, p < 0.001, respectively), and negative correlation with SOD (r = 0.87, p < 0.01). Conclusion and Perspective: Our results indicated that, leukocytes DNA damage and oxidative stress were significantly higher in lymphoma patients, suggesting that the direct effect of chemotherapy and the alteration of the redox balance may influence oxidative/antioxidative status.

Keywords: chemotherapy, comet assay, DNA damage, lymphoma

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Authors: Jamuna Rajeswaran

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In the past two decades, with a population of more than a billion. India is passing through a major socio-demographic and epidemiological transition with consequent changes in health scenario. TBI constitute significant burden on health care resources in India The impact on a person and family can be devastating. Patients with TBI experience persistent cognitive deficits, emotional changes, which contribute to the disruption of life activities. The recovery of TBI would be maximized by appropriate rehabilitation. Neurofeedback is an emerging neuroscience-based clinical application. Sixty patients were recruited for this study after obtaining informed consent. Rivermead Head Injury Follow-up Questionnaire, Rivermead Post Concussion Symptoms Questionnaire and Visual Analog Scale were used to assess the behavioral and symptomotolgy associated with post TBI. Neuropsychological assessment was carried out using NIMHANS neuropsychological battery 2004. The Intervention group received neurofeedback training and the waitlist group did not receive any treatment during this phase. Patients were allocated to intervention and waitlist group at random. There were 30 patients in each group. Patients were given 20 sessions of NFT Patients were trained on the O1 and O2 channels for alpha theta training. Each session was of 40 minutes duration with 5-6 sessions per week. The post-training assessment was carried out for the intervention group after 20 sessions of NFT. The waitlist group underwent assessment after one month. Results showed neurofeedback training is effective in ameliorating deficits in cognitive functions and quality of life in patients with TBI. Improvements were corroborated by the clinical interview with patients and significant others post NFT.

Keywords: assessment, rehabilitation, cognition, EEG neurofeedback

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Authors: Swathi Gopakumar, Sruthi Krishna, Shivasubramani Krishnamoorthy

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Contactless, painless and radiation-free thermal imaging technology is one of the preferred screening modalities for detection of breast cancer. However, poor signal to noise ratio and the inexorable need to preserve edges defining cancer cells and normal cells, make the segmentation process difficult and hence unsuitable for computer-aided diagnosis of breast cancer. This paper presents key findings from a research conducted on the appraisal of two promising techniques, for the detection of breast cancer: (I) marker-controlled, Level-set segmentation of anisotropic diffusion filtered preprocessed image versus (II) Segmentation using marker-controlled level-set on a Gaussian-filtered image. Gaussian-filtering processes the image uniformly, whereas anisotropic filtering processes only in specific areas of a thermographic image. The pre-processed (Gaussian-filtered and anisotropic-filtered) images of breast samples were then applied for segmentation. The segmentation of breast starts with initial level-set function. In this study, marker refers to the position of the image to which initial level-set function is applied. The markers are generally placed on the left and right side of the breast, which may vary with the breast size. The proposed method was carried out on images from an online database with samples collected from women of varying breast characteristics. It was observed that the breast was able to be segmented out from the background by adjustment of the markers. From the results, it was observed that as a pre-processing technique, anisotropic filtering with level-set segmentation, preserved the edges more effectively than Gaussian filtering. Segmented image, by application of anisotropic filtering was found to be more suitable for feature extraction, enabling automated computer-aided diagnosis of breast cancer.

Keywords: anisotropic diffusion, breast, Gaussian, level-set, thermograms

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Authors: Ilzira A. Minigalieva, Tatiana V. Bushueva, Eleonore Frohlich, Vladimir Panov, Ekaterina Shishkina, Boris A. Katsnelson

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Background: The overwhelming majority of the experimental studies in the field of metal nanotoxicology have been performed on cultures of established cell lines, with very few researchers focusing on animal experiments, while a juxtaposition of conclusions inferred from these two types of research is blatantly lacking. The least studied aspect of this problem relates to characterizing and predicting the combined toxicity of metallic nanoparticles. Methods: Comparative and combined toxic effects of purposefully prepared spherical NiO and Mn₃O₄ nanoparticles (mean diameters 16.7 ± 8.2 nm and 18.4 ± 5.4 nm respectively) were estimated on cultures of human cell lines: MRC-5 fibroblasts, THP-1 monocytes, SY-SY5Y neuroblastoma cells, as well as on the latter two lines differentiated to macrophages and neurons, respectively. The combined cytotoxicity was mathematically modeled using the response surface methodology. Results: The comparative assessment of the studied NPs unspecific toxicity previously obtained in vivo was satisfactorily reproduced by the present in vitro tests. However, with respect to manganese-specific brain damage which had been demonstrated by us in animal experiment with the same NPs, the testing on neuronall cell culture showed only a certain enhancing effect of Mn₃O₄-NPs on the toxic action of NiO-NPs, while the role of the latter prevailed. Conclusion: From the point of view of the preventive toxicology, the experimental modeling of metallic NPs combined toxicity on cell cultures can give non-reliable predictions of the in vivo action’s effects.

Keywords: manganese oxide, nickel oxide, nanoparticles, in vitro toxicity

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Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

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Authors: Mohammad Rawashdeh, Mark McEntee, Maha Zaitoun, Mostafa Abdelrahman, Patrick Brennan, Haytham Alewaidat, Sarah Lewis, Charbel Saade

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Despite the tremendous advancements that have been generated by Computed Tomography (CT) in the field of diagnosis, concerns have been raised about the potential cancer induction risk from CT because of the exponentially increased use of it in medicine. This study aims at investigating the application and knowledge of practicing radiographers in Jordan about CT radiation. In order to collect the primary data of this study, a questionnaire was designed and distributed by social media using a snow-balling sampling method. The respondents (n=54) have answered 36 questions including the questions about their demographic information, knowledge about Diagnostic Reference Levels (DRLs), CT exposure and adaptation of pediatric patients exposure. The educational level of the respondents was either at a diploma degree (35.2%) or bachelor (64.8%). The results of this study have indicated a good level of general knowledge between radiographers about the relationship between image quality, exposure parameters, and patient dose. The level of knowledge related to DRL was poor where less than 7.4 percent of the sample members were able to give specific values for a number of common anatomical fields, including abdomen, brain, and chest. Overall, Jordanian radiographers need to gain more knowledge about the expected levels of the dose when applying good practice. Additional education on DRL or DRL inclusion in educational programs is highlighted.

Keywords: computed tomography, CT scan, DRLs, exposure parameters, image quality, radiation dose

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Authors: Yasaman Mohammadi

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Executive functions are a critical component of goal-directed behavior, encompassing a diverse set of cognitive processes such as working memory, cognitive flexibility, and inhibitory control. These functions are known to decline with age, but the precise mechanisms underlying this decline remain unclear. This paper provides an in-depth review of recent research investigating age-related changes in executive functions, drawing on insights from neuroimaging, genetics, and cognitive neuroscience. Through an interdisciplinary approach, this paper offers a nuanced understanding of the complex interplay between neural mechanisms, genetic factors, and cognitive processes that contribute to executive function decline in aging. Here, we investigate how different neuroimaging methods, like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), have helped scientists better understand the brain bases for age-related declines in executive function. Additionally, we discuss the role of genetic factors in mediating individual differences in executive functions across the lifespan, as well as the potential for cognitive interventions to mitigate age-related decline. Overall, this paper presents a comprehensive and integrative view of the current state of knowledge regarding age-related changes in executive functions. It underscores the need for continued interdisciplinary research to fully understand the complex and dynamic nature of executive function decline in aging, with the ultimate goal of developing effective interventions to promote healthy cognitive aging.

Keywords: executive functions, aging, neuroimaging, cognitive neuroscience, working memory, cognitive training

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Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

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Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

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Authors: Azza EL-Medany, Jamila EL-Medany

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Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present work studied the effect of green tea extract on bleomycin–induced lung fibrosis in rats. Animals were divided into three groups: (1) Saline control group; (2) bleomycin group in which rats were injected with bleomycin (15mg/kg,i.p.) three times a week for four weeks; (3) bleomycin and green tea group in which green tea extract was given to rats (100mg/kg/day, p.o) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the experiment. Bleomycin–induced pulmonary injury and lung fibrosis that was indicated by increased lung hydroxyproline content, elevated nitric oxide synthase, myeoloperoxidase (MPO), platelet activating factor (PAF), tumor necrosis factor α (TNF_α), transforming growth factor 1β (TGF1β) and angiotensin converting enzyme (ACE) activity in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration (GSH). Moreover, bleomycin resulted in a severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and green tea extract reduced bleomycin–induced lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, levels of MPO, PAF, TNF-α, and ACE in lung tissues. Furthermore, green tea extract ameliorated bleomycin– induced reduction in GSH concentration. Finally, histological evidence supported the ability of green tea extract to attenuate bleomycin–induced lung fibrosis and consolidation. Thus, the finding of the present study provides that green tea may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Keywords: bleomycin, lung fibrosis, green tea, oxygen species

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Authors: Anthony Townsend, Robyn Fasser

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While complete objectivity is a desirable scientific position from which to conduct a care and contact evaluation (CCE), it is precisely the recognition that we are inherently incapable of operating objectively that is the foundation of ethical practice and skilled assessment. Drawing upon recent research from Daniel Kahneman (2021) on the differences between noise and bias, as well as different inherent biases collectively termed “The Elephant in the Brain” by Kevin Simler and Robin Hanson (2019) from Oxford University, this presentation addresses both the various ways in which our judgments, perceptions and even procedures can be distorted and contaminated while conducting a CCE, but also considers the value of second order cybernetics and the psychodynamic concept of ‘ambivalence’ as a conceptual basis to inform our assessment methodologies to limit such errors or at least better identify them. Both a conceptual framework for ambivalence, our higher-order capacity to allow for the convergence and consideration of multiple emotional experiences and cognitive perceptions to inform our reasoning, and a practical methodology for assessment relying on data triangulation, Bayesian inference and hypothesis testing is presented as a means of promoting ethical practice for health care professionals conducting CCEs. An emphasis on widening awareness and perspective, limiting ‘splitting’, is demonstrated both in how this form of emotional processing plays out in alienating dynamics in families as well as the assessment thereof. In addressing this concept, this presentation aims to illuminate the value of ambivalence as foundational to ethical practice for assessors.

Keywords: ambivalence, forensic, psychology, noise, bias, ethics

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Authors: Masica Jordan Alston, Angela N. Bullock, Angela S. Henderson, Stephanie Strianse, Sade Dunn, Joseph Hackett, Alaysia Black Hackett, Marcus Mason

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The Energy Model of Cumulative Grief was created in 2018. The Energy Model of Cumulative Grief utilizes historic models of grief stage theories. The innovative model is additionally unique due to its focus on cultural responsiveness. The Energy Model of Cumulative Grief helps to train practitioners who work with clients dealing with grief and loss. This paper assists in introducing the world to this innovative model and exploring how this model positively impacted a convenience sample of 140 practitioners and individuals experiencing grief and loss. Respondents participated in Webinars provided by the National Grief and Loss Center of America (NGLCA). Participants in this cross-sectional research design study completed one of three Grief and Loss Surveys created by the Grief and Loss Centers of America. Data analysis for this study was conducted via SPSS and Survey Hero to examine survey results for respondents. Results indicate that the Energy Model of Cumulative Grief was an effective resource for participants in addressing grief and loss. The majority of participants found the Webinars to be helpful and a conduit to providing them with higher levels of hope. The findings suggest that using The Energy Model of Cumulative Grief is effective in providing culturally responsive grief and loss resources to practitioners and clients. There are far reaching implications with the use of technology to provide hope to those suffering from grief and loss worldwide through The Energy Model of Cumulative Grief.

Keywords: grief, loss, grief energy, grieving brain

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Authors: Ibrahim Nadeem, Mohammed Rahman, Yasser Ad-Dab’Bagh, Mahmood Akhtar

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Depression is one of the most prevalent mental illnesses and is often associated with various other medical disorders. In this review, we aim to evaluate existing systematic reviews that investigate the use of probiotics as a treatment for depressive symptoms. Five online databases were searched for relevant studies up to December 2017. Systematic reviews that included randomized controlled trials assessing the efficacy of probiotics in the treatment of depressive symptoms were included. Seven systematic reviews met the inclusion criteria. Three of these reviews conducted meta-analyses, out of which, two found probiotics to significantly improve depressive symptoms in the sample population. Two meta-analyses conducted subgroup analysis based on health status, and both found probiotics to significantly decrease depressive symptoms in patients with major depressive disorder, but only one review found it to significantly decrease in healthy patients. Another subgroup analysis was conducted based on age, and found probiotics to produce significant effects on subjects under the age of 60, but close to no effect on patients over the age of 65. Out of the four reviews that conducted qualitative analysis, three reviews concluded that probiotics have the potential to be used as a treatment. Due to the differences in clinical trials, a definitive effect of probiotics on depressive symptoms cannot be concluded. Nonetheless, probiotics seem to produce a significant therapeutic effect for subjects with pre-existing depressive symptoms. Further studies are warranted for definitive conclusions.

Keywords: depression, gut-brain axis, gut microbiota, probiotic, psychobiotic

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Authors: Nasreen Basoudan, Andrea Tales, Frederic Boy

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Non-clinical anxiety may be comprised of state anxiety - temporarily experienced anxiety related to a specific situation, and trait anxiety - a longer lasting response or a general disposition to anxiety. While temporary and occasional anxiety whether as a mood state or personality dimension is normal, nonclinical anxiety may influence many more components of information processing than previously recognized. In ageing and dementia-related research, disease characterization now involves attempts to understand a much wider range of brain function such as loss of inhibitory control, as against the more common focus on memory and cognition. However, in many studies, the tendency has been to include individuals with clinical anxiety disorders while excluding persons with lower levels of state or trait anxiety. Loss of inhibitory cognitive control can lead to behaviors such as aggression, reduced sensitivity to others, sociopathic thoughts and actions. Anxiety has also been linked to inhibitory control, with research suggesting that people with anxiety are less capable of inhibiting their emotions than the average person. This study investigates the relationship between anxiety and loss of inhibitory control in younger and older adults, using a variety of questionnaires and computers-based tests. Based on the premise that irrespective of classification, anxiety is associated with a wide range of physical, affective, and cognitive responses, this study explores evidence indicative of the potential influence anxiety per se on loss of inhibitory control, in order to contribute to discussion and appropriate consideration of anxiety-related factors in methodological practice.

Keywords: anxiety, ageing, dementia, inhibitory control

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

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Authors: Hitesh Gupta, Surender Dabas

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TORS is increasingly gaining widespread use and has been explored as minimally invasive surgery for the treatment of supraglottic cancer (SGC). Being a central critical role of Supraglottis in deglutition, swallowing outcomes post TORS remain a most important factor. Available published studies show inconsistent swallowing outcomes and are deficient in standardized outcome measures, description of swallowing recovery and rehabilitation. So, the objective of this study is to find out swallowing outcomes in SGC patients after TORS provided with early dysphagia management using standardized measures. Prospectively 16 patients were recruited in the study who underwent TORS for primary tumor of Supraglottis, involving one or more sub-sites or invading to sites other than Supraglottis at the BLK Super Specialty Hospital, New Delhi from March 2019 to June 2020. All patients were evaluated for dysphagia with subsequent swallowing rehabilitation on post operative day 3 in the hospital or at the time of discharge, whichever was earlier. Functional oral intake scale (FOIS) and penetration-aspiration score (PAS) were used as outcome measures to quantify swallowing recovery at one month and six month post operatively. Post TORS, patients achieved functional swallow in less than one month, where resection was limited to Supraglottis, while the recovery was delayed in patients with extended resection to tongue base or hypopharynx. Overall, out of Total 16 cases including all supraglottis sub-catagories, 13 (81%) could remove their NG tube (FOIS ≥5 and PAS=1 ) within 6 months. In which 8 cases(62%) achieved functional swallow in less than one month. Swallowing outcomes post TORS supraglottic laryngectomy are favorable if provided with early dysphagia management (or swallowing rehabilitation).

Keywords: dysphagia, supraglottic cancer, swallowing, TORS

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Ebele V. Okoli, Emmanuel Nwobi, Dozie Ezechukwu, Ijeoma Itanyi

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One in seven people worldwide suffer from a disability. 80% of people with disabilities live in developing countries. Negative attitudes and misconceptions among health-care providers constitute barri¬ers to optimal health care for people with disabilities. This underscores the relevance of a study of the attitude of Nigerian medical students towards disability and their willingness to work in the disability sector. This was a descriptive cross-sectional study conducted among 254 penultimate and final year medical students of a university in southeastern Nigeria. The mean age of the students was 24.8 ± 3.12 years. Majority of the students were male (75.2%), single (96.9%), of the Igbo tribe (86.6%), Christian (97.6%) and grew up in urban areas (68.1%). Results indicated that the medical students had a predominantly positive attitude towards people with disability as 73.8% had a positive attitude and mean attitude score was 67.03 ± 0.14 (positive attitude = 61 – 120, negative attitude = 0 - 60). Chi-square analysis did not show any significant effect of demographic and social factors on the students’ attitude towards People with Disabilities. The students were mostly willing to work in areas that address the challenges of people with disability (70.4%) but a greater proportion had never heard about Disability Studies (67.5%). About a third of the students (33.2%) would like to travel abroad to practice in the disability sector. Conclusions: The students generally had a positive attitude towards people with disability and a greater percentage were willing to work in the disability sector in their future career. About two-thirds had however, never heard about disability studies. There was some potential for brain drain among the students as a third of the population intended to practice abroad on graduation.

Keywords: attitudes, career interest, disability, medical students

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Authors: Yu-Chu Yeh, WeiChin Hsu, Chih-Yen Chang

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Substitution, combination, modification, putting to other uses, elimination, and rearrangement (SCAMPER) has been regarded as an effective technique that provides a structured way to help people to produce creative ideas and solutions. Although some neuroscience studies regarding creativity training have been conducted, no study has focused on SCAMPER. This study therefore aimed at examining whether the learning of SCAMPER through video tutorials would result in alternations of neural activation. Thirty college students were randomly assigned to the experimental group or the control group. The experimental group was requested to watch SCAMPER videos, whereas the control group was asked to watch natural-scene videos which were regarded as neutral stimulating materials. Each participant was brain scanned in a Functional magnetic resonance imaging (fMRI) machine while undertaking a creativity test before and after watching the videos. Furthermore, a two-way ANOVA was used to analyze the interaction between groups (the experimental group; the control group) and tasks (C task; M task; X task). The results revealed that the left precuneus significantly activated in the interaction of groups and tasks, as well as in the main effect of group. Furthermore, compared with the control group, the experimental group had greater activation in the default mode network (left precuneus and left inferior parietal cortex) and the motor network (left postcentral gyrus and left supplementary area). The findings suggest that the SCAMPER training may facilitate creativity through the stimulation of the default mode network and the motor network.

Keywords: creativity, default mode network, neural activation, SCAMPER

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Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

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Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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