Search results for: brain tumor
1436 Cell Elevator: A Novel Technique for Cell Sorting and Circulating Tumor Cell Detection and Discrimination
Authors: Kevin Zhao, Norman J. Horing
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A methodology for cells sorting and circulating tumor cell detection and discrimination is presented in this paper. The technique is based on Dielectrophoresis and microfluidic device theory. Specifically, the sorting of the cells is realized by adjusting the relation among the sedimentation forces, the drag force provided by the fluid, and the Dielectrophortic force that is relevant to the bias voltage applied on the device. The relation leads to manipulation of the elevation of the cells of the same kind to a height by controlling the bias voltage. Once the cells have been lifted to a position next to the bottom of the cell collection channel, the buffer fluid flashes them into the cell collection channel. Repeated elevation of the cells leads to a complete sorting of the cells in the sample chamber. A proof-of-principle example is presented which verifies the feasibility of the methodology.Keywords: cell sorter, CTC cell, detection and discrimination, dielectrophoresisords, simulation
Procedia PDF Downloads 4321435 Can Demyelinative Lesion Cause To Behaviora Change?
Authors: Arezou Hajhashemi, Karim Asgari, Masoud Etemadifar, Maryam Keyvani, Ali Hekmatnia
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Multiple Sclerosis (MS) is one of the most prevalent demyelinating diseases in CNS. As in other chronic cerebral diseases, impairment in cognitive functioning and in memory is popular. Because of the inflammatory and demyelinating nature of the disease, the localization of plaques in different parts of the Prefrontal and Limbic System, may lead to memorial symptoms. This investigation was intended to study relationship between frequency of plaques and memorial symptoms arising from dysfunction limbic system and prefrontal of patients with MS. The sample was selected randomly from patients with MS with memory problem, who have been referred to Isfahan Multiple Sclerosis Society. Brain System Test and Memory Test was administered to the sample, and their MRI's were analyzed by specialist in order to indentify two different parts of plaques. The data was analyzed by SPSS. The results showed that there were significant relationship between MS plaques and prefrontal's dysfunction and memorial symptom related to prefrontal area; however, there were no significant relationship between MS plaques and limbic system's dysfunction and memorial symptoms related to limbic system area. The results of this study suggest that memorial symptoms due to injury regions of the brain have the most significant relationship to prefrontal. Better judgment about these results needs more studies in future.Keywords: multiple sclerosis, magnetic image, brain injury, behavior disorder
Procedia PDF Downloads 5131434 Prognostic Significance of Nuclear factor kappa B (p65) among Breast Cancer Patients in Cape Coast Teaching Hospital
Authors: Precious Barnes, Abraham Mensah, Leonard Derkyi-Kwarteng, Benjamin Amoani, George Adjei, Ernest Adankwah, Faustina Pappoe, Kwabena Dankwah, Daniel Amoako-Sakyi, Samuel Victor Nuvor, Dorcas Obiri-Yeboah, Ewura Seidu Yahaya, Patrick Kafui Akakpo, Roland Osei Saahene
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Context: Breast cancer is a prevalent and aggressive type of cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) is a transcription factor that has been associated with tumor progression in breast cancer. However, there is a lack of published data on NF-kB in breast cancer patients in Ghana or other African countries. Research Aim: The aim of this study was to assess the prognostic significance of NF-kB (p65) expression and its association with various clinicopathological features in breast cancer patients at the Cape Coast Teaching Hospital in Ghana. Methodology: A total of 90 formalin-fixed breast cancer tissues and 15 normal breast tissues were used in this study. The expression level of NF-kB (p65) was examined using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Findings: The study found that NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High-level expression of NF-kB (p65) was more common in tumor grade 3 compared to grade 1, and Ki67 > 20 had higher expression of NF-kB (p65) compared to Ki67 ≤ 20. Triple-negative breast cancer patients had the highest overexpression of NF-kB (p65) compared to other molecular subtypes. There was no significant association between NF-kB (p65) expression and other clinicopathological parameters. Theoretical Importance: This study provides important insights into the expression of NF-kB (p65) in breast cancer patients in Ghana, particularly in relation to tumor grade and proliferation index. The findings suggest that NF-kB (p65) could serve as a potential biological marker for cancer stage, progression, prognosis and as a therapeutic target. Data Collection and Analysis Procedures: Formalin-fixed breast cancer tissues and normal breast tissues were collected and analyzed using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Question Addressed: This study addressed the question of the prognostic significance of NF-kB (p65) expression and its association with clinicopathological features in breast cancer patients in Ghana. Conclusion: This study, the first of its kind in Ghana, demonstrates that NF-kB (p65) is highly expressed among breast cancer patients at the Cape Coast Teaching Hospital, especially in triple-negative breast cancer patients. The expression of NF-kB (p65) is associated with tumor grade and proliferation index. NF-kB (p65) could potentially serve as a biological marker for cancer stage, progression, prognosis, and as a therapeutic target.Keywords: breast cancer, Ki67, NF-kB (p65), tumor grade
Procedia PDF Downloads 701433 A Time and Frequency Dependent Study of Low Intensity Microwave Radiation Induced Endoplasmic Reticulum Stress and Alteration of Autophagy in Rat Brain
Authors: Ranjeet Kumar, Pravin Suryakantrao Deshmukh, Sonal Sharma, Basudev Banerjee
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With the tremendous increase in exposure to radiofrequency microwaves emitted by mobile phones, globally public awareness has grown with regard to the potential health hazards of microwaves on the nervous system in the brain. India alone has more than one billion mobile users out of 4.3 billion globally. Our studies have suggested that radio frequency able to affect neuronal alterations in the brain, and hence, affecting cognitive behaviour. However, adverse effect of low-intensity microwave exposure with endoplasmic reticulum stress and autophagy has not been evaluated yet. In this study, we explore whether low-intensity microwave induces endoplasmic reticulum stress and autophagy with varying frequency and time duration in Wistar rat. Ninety-six male Wistar rat were divided into 12 groups of 8 rats each. We studied at 900 MHz, 1800 MHz, and 2450 MHz frequency with reference to sham-exposed group. At the end of the exposure, the rats were sacrificed to collect brain tissue and expression of CHOP, ATF-4, XBP-1, Bcl-2, Bax, LC3 and Atg-4 gene was analysed by real-time PCR. Significant fold change (p < 0.05) of gene expression was found in all groups of 1800 MHz and 2450 MHz exposure group in comparison to sham exposure group. In conclusion, the microwave exposure able to induce ER stress and modulate autophagy. ER (endoplasmic reticulum) stress and autophagy vary with increasing frequency as well as the duration of exposure. Our results suggested that microwave exposure is harmful to neuronal health as it induces ER stress and hampers autophagy in neuron cells and thereby increasing the neuron degeneration which impairs cognitive behaviour of experimental animals.Keywords: autophagy, ER stress, microwave, nervous system, rat
Procedia PDF Downloads 1311432 SEM Detection of Folate Receptor in a Murine Breast Cancer Model Using Secondary Antibody-Conjugated, Gold-Coated Magnetite Nanoparticles
Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver
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Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.Keywords: cancer cell, nanoparticles, cell culture, SEM
Procedia PDF Downloads 7321431 Brain Stem Posterior Reversible Encephalopathy Syndrome in Nephrotic Syndrome
Authors: S. H. Jang
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Posterior reversible encephalopathy syndrome (PRES) is characterized by acute neurologic symptoms (visual loss, headache, altered mentality and seizures) and by typical imaging findings (bilateral subcortical and cortical edema with predominatly posterior distribution). Nephrotic syndrome is a syndrome comprising signs of proteinuria, hypoalbuminemia, and edema. It is well known that hypertension predispose patient with nephrotic syndrome to PRES. A 45-year old male was referred for suddenly developed vertigo, disequilibrium. He had previous history of nephrotic syndrome. His medical history included diabetes controlled with medication. He was hospitalized because of generalized edema a few days ago. His vital signs were stable. On neurologic examination, his mental state was alert. Horizontal nystagmus to right side on return to primary position was observed. He showed good grade motor weakness and ataxia in right upper and lower limbs without other sensory abnormality. Brain MRI showed increased signal intensity in FLAIR image, decreased signal intensity in T1 image and focal enhanced lesion in T1 contrast image at whole midbrain, pons and cerebellar peduncle symmetrically, which was compatible with vasogenic edema. Laboratory findings showed severe proteinuria and hypoalbuminemia. He was given intravenous dexamethasone and diuretics to reduce vasogenic edema and raise the intra-vascular osmotic pressure. Nystagmus, motor weakness and limb ataxia improved gradually over 2 weeks; He recovered without any neurologic symptom and sign. Follow-up MRI showed decreased vasogenic edema fairly. We report a case of brain stem PRES in normotensive, nephrotic syndrome patient.Keywords: posterior reversible encephalopathy syndrome, MRI, nephrotic syndrome, vasogenic brain edema
Procedia PDF Downloads 2741430 The Experience of Applying Multi-Sensory Stimulation ICU for Arousing a Patient with Traumatic Brain Injury in Intensive Care
Authors: Hsiao-Wen Tsai
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Motor vehicle accident is the first cause of head injury in the world; severe head injury cases may cause conscious disturbance and death. This is a report about a case of a young adult patient suffering from motor vehicle accident leading to severe head injury who passed through three time surgical procedures, and his mother (who is the informal caregiver). This case was followed from 28th January to 15th February 2011 by using Gordon’s 11 functional health patterns. Patient’s cognitive-perceptual and self-perception-self-concept patterns were altered. Anxiety was also noted on his informal caregiver due to patients’ condition. During the intensive care period, maintaining patient’s vital signs and cerebral perfusion pressure were essential to avoid secondary neuronal injury. Multi-sensory stimulation, caring accompanying, supporting, listening and encouraging patient’s family involved in patient care were very important to reduce informal caregiver anxiety. Finally, the patient consciousness improved from GCS 4 to GCS 11 before discharging from ICU. Patient’s primary informal caregiver, his mother, also showed anxiety improvement. This is was successful case with traumatic brain injury recovered from coma.Keywords: anxiety, multi-sensory stimulation, reduce intracranial adaptive capacity, traumatic brain injury
Procedia PDF Downloads 2671429 Hydrogen, a Novel Therapeutic Molecule, in Osteosarcoma Disease
Authors: Priyanka Sharma, Rajeshwar Nath Srivastava
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Hydrogen has a high level of efficacy in suppressing tumour growth. The role of hydrogen in cancer treatment is unclear. This groundbreaking research will focus on the most effective therapeutic approach for osteosarcoma. Recent data reveals that hydrogen, a naturally occurring gaseous chemical, can protect cells from death. However, little is known about the signalling pathways that regulate cardiac cell death and individual apoptosis signalling by H2 and its downstream targets. According to certain research, the anti-tumor effect of H2 released by magnesium-based biomaterials is mediated by the P53-mediated lysosome-mitochondria apoptosis signalling pathway, bolstering the biomaterial's therapeutic potential as a localised anti-tumor treatment. The role of the H2 molecule in the signalling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in Osteosarcoma is discussed in this paper. Potential Hydrogen-based therapy techniques will broaden the treatment horizon for Osteosarcoma.Keywords: osteosarcoma, metastasis, hhydrogen, therapeutic
Procedia PDF Downloads 1371428 Comparative Study of Outcome of Patients with Wilms Tumor Treated with Upfront Chemotherapy and Upfront Surgery in Alexandria University Hospitals
Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly
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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery
Procedia PDF Downloads 3161427 The Effectiveness of Exercise Therapy on Decreasing Pain in Women with Temporomandibular Disorders and How Their Brains Respond: A Pilot Randomized Controlled Trial
Authors: Zenah Gheblawi, Susan Armijo-Olivo, Elisa B. Pelai, Vaishali Sharma, Musa Tashfeen, Angela Fung, Francisca Claveria
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Due to physiological differences between men and women, pain is experienced differently between the two sexes. Chronic pain disorders, notably temporomandibular disorders (TMDs), disproportionately affect women in diagnosis, and pain severity in opposition of their male counterparts. TMDs are a type of musculoskeletal disorder that target the masticatory muscles, temporalis muscle, and temporomandibular joints, causing considerable orofacial pain which can usually be referred to the neck and back. Therapeutic methods are scarce, and are not TMD-centered, with the latest research suggesting that subjects with chronic musculoskeletal pain disorders have abnormal alterations in the grey matter of their brains which can be remedied with exercise, and thus, decreasing the pain experienced. The aim of the study is to investigate the effects of exercise therapy in TMD female patients experiencing chronic jaw pain and to assess the consequential effects on brain activity. In a randomized controlled trial, the effectiveness of an exercise program to improve brain alterations and clinical outcomes in women with TMD pain will be tested. Women with chronic TMD pain will be randomized to either an intervention arm or a placebo control group. Women in the intervention arm will receive 8 weeks of progressive exercise of motor control training using visual feedback (MCTF) of the cervical muscles, twice per week. Women in the placebo arm will receive innocuous transcutaneous electrical nerve stimulation during 8 weeks as well. The primary outcomes will be changes in 1) pain, measured with the Visual Analogue Scale, 2) brain structure and networks, measured by fractional anisotropy (brain structure) and the blood-oxygen level dependent signal (brain networks). Outcomes will be measured at baseline, after 8 weeks of treatment, and 4 months after treatment ends and will determine effectiveness of MCTF in managing TMD, through improved clinical outcomes. Results will directly inform and guide clinicians in prescribing more effective interventions for women with TMD. This study is underway, and no results are available at this point. The results of this study will have substantial implications on the advancement in understanding the scope of plasticity the brain has in regards with pain, and how it can be used to improve the treatment and pain of women with TMD, and more generally, other musculoskeletal disorders.Keywords: exercise therapy, musculoskeletal disorders, physical therapy, rehabilitation, tempomandibular disorders
Procedia PDF Downloads 2911426 Syndecan -1 as Regulator of Ischemic-Reperfusion Damage Limitation in Experiment
Authors: M. E. Kolpakova, A. A. Jakovleva, L. S. Poliakova, H. El Amghari, S. Soliman, D. R. Faizullina, V. V. Sharoyko
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Brain neuroplasticity is associated with blood-brain barrier vascular endothelial proteoglycans and post-stroke microglial activation. The study of the mechanisms of reperfusion injury limitation by remote ischemic postconditioning (RC) is of interest due to the effects on functional recovery after cerebral ischemia. The goal of the study is the assessment of the role of syndecan-1 (SDC-1) in restriction of ischemic-reperfusion injury on middle cerebral artery model in rats using RC protocol. Randomized controlled trials were conducted. Ischemia was performed by middle cerebral artery occlusion by Belayev L. (1996) on the Wistar rat-males (n= 87) weighting 250 ± 50 g. under general anesthesia (Zoletil 100 и Xylazine 2%). Syndecan-1 (SDC-1) concentration difference in plasma samples of false operated animals and animals with brain ischemia was 30% (30 min. МСАо: 41.4 * ± 1.3 ng/ml). SDC-1 concentration in animal plasma samples with ischemia + RC protocol was 112% (30 min МСАо+ RC): 67.8**± 5.8 ng/ml). Calculation of infarction volume in the ischemia group revealed brain injury in 31.97 ± 2.5%; the volume of infarction was 13.6 ± 1.3% in 30 min. МCАо + RC group. Swelling of tissue in the group 30 min. МCАо + RC was 16 ± 2.1%; it was 47 ± 3.3%. in 30 min. МCАо group. Correlation analysis showed a high direct correlation relationship between infarct area and muscle strength in the right forelimb (КК=0.72) in the 30 min. МCАо + RC group. Correlation analysis showed very high inverse correlation between infarct area and capillary blood flow in the 30 min. МCАо + RC group (p <0.01; r = -0.98). We believe the SDC-1 molecule in blood plasma may play role of potential messenger of ischemic-reperfusion injury restriction mechanisms. This leads to infarct-limiting effect of remote ischemic postconditioning and early functioning recovery.Keywords: ischemia, МСАо, remote ischemic postconditioning, syndecan-1
Procedia PDF Downloads 591425 lncRNA Gene Expression Profiling Analysis by TCGA RNA-Seq Data of Breast Cancer
Authors: Xiaoping Su, Gabriel G. Malouf
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Introduction: Breast cancer is a heterogeneous disease that can be classified in 4 subgroups using transcriptional profiling. The role of lncRNA expression in human breast cancer biology, prognosis, and molecular classification remains unknown. Methods and results: Using an integrative comprehensive analysis of lncRNA, mRNA and DNA methylation in 900 breast cancer patients from The Cancer Genome Atlas (TCGA) project, we unraveled the molecular portraits of 1,700 expressed lncRNA. Some of those lncRNAs (i.e, HOTAIR) are previously reported and others are novel (i.e, HOTAIRM1, MAPT-AS1). The lncRNA classification correlated well with the PAM50 classification for basal-like, Her-2 enriched and luminal B subgroups, in contrast to the luminal A subgroup which behaved differently. Importantly, estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Gene set enrichment analysis for cis- and trans-acting lncRNA showed enrichment for breast cancer signatures driven by breast cancer master regulators. Almost two third of those lncRNA were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that lncRNA expression may result in increased activity of neighboring genes. Differential analysis of gene expression profiling data showed that lncRNA HOTAIRM1 was significantly down-regulated in basal-like subtype, and DNA methylation profiling data showed that lncRNA HOTAIRM1 was highly methylated in basal-like subtype. Thus, our integrative analysis of gene expression and DNA methylation strongly suggested that lncRNA HOTAIRM1 should be a tumor suppressor in basal-like subtype. Conclusion and significance: Our study depicts the first lncRNA molecular portrait of breast cancer and shows that lncRNA HOTAIRM1 might be a novel tumor suppressor.Keywords: lncRNA profiling, breast cancer, HOTAIRM1, tumor suppressor
Procedia PDF Downloads 1041424 Stimulus-Response and the Innateness Hypothesis: Childhood Language Acquisition of “Genie”
Authors: Caroline Kim
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Scholars have long disputed the relationship between the origins of language and human behavior. Historically, behaviorist psychologist B. F. Skinner argued that language is one instance of the general stimulus-response phenomenon that characterizes the essence of human behavior. Another, more recent approach argues, by contrast, that language is an innate cognitive faculty and does not arise from behavior, which might develop and reinforce linguistic facility but is not its source. Pinker, among others, proposes that linguistic defects arise from damage to the brain, both congenital and acquired in life. Much of his argument is based on case studies in which damage to the Broca’s and Wernicke’s areas of the brain results in loss of the ability to produce coherent grammatical expressions when speaking or writing; though affected speakers often utter quite fluent streams of sentences, the words articulated lack discernible semantic content. Pinker concludes on this basis that language is an innate component of specific, classically language-correlated regions of the human brain. Taking a notorious 1970s case of linguistic maladaptation, this paper queries the dominant materialist paradigm of language-correlated regions. Susan “Genie” Wiley was physically isolated from language interaction in her home and beaten by her father when she attempted to make any sort of sound. Though without any measurable resulting damage to the brain, Wiley was never able to develop the level of linguistic facility normally achieved in adulthood. Having received a negative reinforcement of language acquisition from her father and lacking the usual language acquisition period, in adulthood Wiley was able to develop language only at a quite limited level in later life. From a contemporary behaviorist perspective, this case confirms the possibility of language deficiency without brain pathology. Wiley’s potential language-determining areas in the brain were intact, and she was exposed to language later in her life, but she was unable to achieve the normal level of communication skills, deterring socialization. This phenomenon and others like it in the case limited literature on linguistic maladaptation pose serious clinical, scientific, and indeed philosophical difficulties for both of the major competing theories of language acquisition, innateness, and linguistic stimulus-response. The implications of such cases for future research in language acquisition are explored, with a particular emphasis on the interaction of innate capacity and stimulus-based development in early childhood.Keywords: behaviorism, innateness hypothesis, language, Susan "Genie" Wiley
Procedia PDF Downloads 2911423 Human TP53 Three Dimentional (3D) Core Domain Hot Spot Mutations at Codon, 36, 72 and 240 are Associated with Oral Squamous Cell Carcinoma
Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar
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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure
Procedia PDF Downloads 3651422 Improved Approach to the Treatment of Resistant Breast Cancer
Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova
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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy
Procedia PDF Downloads 2721421 Emotion Processing Differences Between People
Authors: Elif Unveren, Ozlem Bozkurt
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Emotion processing happens when someone has a negative, stressful experience and gets over it in time, and it is a different experience for every person. As to look into emotion processing can be categorised by intensity, awareness, coordination, speed, accuracy and response. It may vary depending on people’s age, sex and conditions. Each emotion processing shows different activation patterns in different brain regions. Activation is significantly higher in the right frontal areas. The highest activation happens in extended frontotemporal areas during the processing of happiness, sadness and disgust. Those emotions also show widely disturbed differences and get produced earlier than anger and fear. For different occasions, listed variables may have less or more importance. A borderline personality disorder is a condition that creates an unstable personality, sudden mood swings and unpredictability of actions. According to a study that was made with healthy people and people who had BPD, there were significant differences in some categories of emotion processing, such as intensity, awareness and accuracy. According to another study that was made to show the emotional processing differences between puberty and was made for only females who were between the ages of 11 and 17, it was perceived that for different ages and hormone levels, different parts of the brain are used to understand the given task. Also, in the different study that was made for kids that were between the age of 4 and 15, it was observed that the older kids were processing emotion more intensely and expressing it to a greater extent. There was a significant increase in fear and disgust in those matters. To sum up, we can say that the activity of undertaking negative experiences is a unique thing for everybody for many different reasons.Keywords: age, sex, conditions, brain regions, emotion processing
Procedia PDF Downloads 831420 Computational Cell Segmentation in Immunohistochemically Image of Meningioma Tumor Using Fuzzy C-Means and Adaptive Vector Directional Filter
Authors: Vahid Anari, Leila Shahmohammadi
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Diagnosing and interpreting manually from a large cohort dataset of immunohistochemically stained tissue of tumors using an optical microscope involves subjectivity and also is tedious for pathologist specialists. Moreover, digital pathology today represents more of an evolution than a revolution in pathology. In this paper, we develop and test an unsupervised algorithm that can automatically enhance the IHC image of a meningioma tumor and classify cells into positive (proliferative) and negative (normal) cells. A dataset including 150 images is used to test the scheme. In addition, a new adaptive color image enhancement method is proposed based on a vector directional filter (VDF) and statistical properties of filtering the window. Since the cells are distinguishable by the human eye, the accuracy and stability of the algorithm are quantitatively compared through application to a wide variety of real images.Keywords: digital pathology, cell segmentation, immunohistochemically, noise reduction
Procedia PDF Downloads 651419 Computational Fluid Dynamics Study of the Effects of Mechanical Forces in Cerebral Aneurysms
Authors: Hashem Al Argha
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Cerebral Aneurysms are the ballooning and defect that occurs in the arteries of the brain. This ballooning might enlarge in size due to mechanical forces and could lead to rupture and death. Computational Fluid Dynamics has been used in the recent years in creating a link between engineering sciences and medical sciences. In this paper, the effects of mechanical forces on cerebral aneurysms will be studied. Results of this study show that mechanical forces could lead to rupture of the aneurysm and could lead to death. High mechanical forces including stresses up to 1.7 MPa could pop aneurysms and lead to a brain hemorrhage.Keywords: computational fluid dynamics, numerical, aneurysm, mechanical forces
Procedia PDF Downloads 2541418 Silymarin Reverses Scopolamine-Induced Memory Deficit in Object Recognition Test in Rats: A Behavioral, Biochemical, Histopathological and Immunohistochemical Study
Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid
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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine
Procedia PDF Downloads 1371417 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice
Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal
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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.Keywords: CRISPR, nanoparticles, brain diseases, administration routes
Procedia PDF Downloads 991416 Navigating Neural Pathways to Success with Students on the Autism Spectrum
Authors: Panda Krouse
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This work is a marriage of the science of Applied Behavioral Analysis and an educator’s look at Neuroscience. The focus is integrating what we know about the anatomy of the brain in autism and evidence-based practices in education. It is a bold attempt to present links between neurological research and the application of evidence-based practices in education. In researching for this work, no discovery of articles making these connections was made. Consideration of the areas of structural differences in the brain are aligned with evidence-based strategies. A brief literary review identifies how identified areas affect overt behavior, which is what, as educators, is what we can see and measure. Giving further justification and validation of our practices in education from a second scientific field is significant for continued improvement in intervention for students on the autism spectrum.Keywords: autism, evidence based practices, neurological differences, education intervention
Procedia PDF Downloads 621415 Review and Evaluation of Trending Canonical Correlation Analyses-Based Brain Computer Interface Methods
Authors: Bayar Shahab
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The fast development of technology that has advanced neuroscience and human interaction with computers has enabled solutions to various problems, and issues of this new era have been found and are being found like no other time in history. Brain-computer interface so-called BCI has opened the door to several new research areas and have been able to provide solutions to critical and important issues such as supporting a paralyzed patient to interact with the outside world, controlling a robot arm, playing games in VR with the brain, driving a wheelchair or even a car and neurotechnology enabled the rehabilitation of the lost memory, etc. This review work presents state-of-the-art methods and improvements of canonical correlation analyses (CCA), which is an SSVEP-based BCI method. These are the methods used to extract EEG signal features or, to be said in a different way, the features of interest that we are looking for in the EEG analyses. Each of the methods from oldest to newest has been discussed while comparing their advantages and disadvantages. This would create a great context and help researchers to understand the most state-of-the-art methods available in this field with their pros and cons, along with their mathematical representations and usage. This work makes a vital contribution to the existing field of study. It differs from other similar recently published works by providing the following: (1) stating most of the prominent methods used in this field in a hierarchical way (2) explaining pros and cons of each method and their performance (3) presenting the gaps that exist at the end of each method that can open the understanding and doors to new research and/or improvements.Keywords: BCI, CCA, SSVEP, EEG
Procedia PDF Downloads 1431414 Anti-Prostate Cancer Effect of GV-1001, a Novel Gonadotropin-Releasing Hormone Receptor Ligand
Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang
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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.Keywords: GV-1001, GnRH, hTERT, prostate cancer
Procedia PDF Downloads 3681413 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital
Authors: Rizwan Iqbal
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Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.Keywords: urology, bladder cancer, turbt, cancer
Procedia PDF Downloads 611412 Characterization of Herberine Hydrochloride Nanoparticles
Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang
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A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer
Procedia PDF Downloads 1211411 Logical Thinking: A Surprising and Promising Insight for Creative and Critical Thinkers
Authors: Luc de Brabandere
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Searchers in various disciplines have long tried to understand how a human being thinks. Most of them seem to agree that the brain works in two very different modes. For us, the first phase of thought imagines, diverges, and unlocks the field of possibilities. The second phase, judges converge and choose. But if we were to stop there, that would give the impression that thought is essentially an individual effort that seldom depends on context. This is, however, not the case. Whether we be a champion in creativity, so primarily in induction, or a master in logic where we are confronted with reality, the ideas we layout are indeed destined to be presented to third parties. They should therefore be exposed, defended, communicated, negotiated, or even sold. Regardless of the quality of the concepts we craft (creative thinking) and the interferences we build (logical thinking) we will take one day, or another, be confronted by people whose beliefs, opinions and ideas differ from ours (critical thinking). Logic and critique: The shared characteristics of logical and critical thoughts include a three-level structure of reasoning invented by the Greeks. For the first time in history, Aristotle tried to model thought deployable in three stages: the concept, the statement, and the reasoning. The three levels can be assessed according to different criteria. A concept is more or less useful, a statement is true or false, and reasoning is right or wrong. This three-level structure allows us to differentiate logic and critique, where the intention and words used are not the same. Logic only deals with the structure of reasoning and exhausts the problem. It regards premises as acquired and excludes the debate. Logic is in all certainty and pursues the truth. Critique is most probably searching for the plausible. Logic and creativity: Many known models present the brain as a two-stroke engine (divergence vs convergence, fast vs. slow, left-brain vs right-brain, Yin vs Yang, etc.). But that’s not the only thing. “Why didn’t we think of that before?” How often have we heard that sentence? A creative idea is the outcome of logic, but you can only understand it afterward! Through the use of exercises, we will witness how logic and creativity work together. A third theme is hidden behind the two main themes of the conference: logical thought, which the author can shed some light on.Keywords: creativity, logic, critique, digital
Procedia PDF Downloads 871410 Cytology Is a Promising Tool for the Diagnosis of High-Grade Serous Ovarian Carcinoma from Ascites
Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika
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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2
Procedia PDF Downloads 1851409 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries
Authors: Janneth Gonzalez, Marco Avila, George Barreto
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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics
Procedia PDF Downloads 3411408 Towards Real-Time Classification of Finger Movement Direction Using Encephalography Independent Components
Authors: Mohamed Mounir Tellache, Hiroyuki Kambara, Yasuharu Koike, Makoto Miyakoshi, Natsue Yoshimura
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This study explores the practicality of using electroencephalographic (EEG) independent components to predict eight-direction finger movements in pseudo-real-time. Six healthy participants with individual-head MRI images performed finger movements in eight directions with two different arm configurations. The analysis was performed in two stages. The first stage consisted of using independent component analysis (ICA) to separate the signals representing brain activity from non-brain activity signals and to obtain the unmixing matrix. The resulting independent components (ICs) were checked, and those reflecting brain-activity were selected. Finally, the time series of the selected ICs were used to predict eight finger-movement directions using Sparse Logistic Regression (SLR). The second stage consisted of using the previously obtained unmixing matrix, the selected ICs, and the model obtained by applying SLR to classify a different EEG dataset. This method was applied to two different settings, namely the single-participant level and the group-level. For the single-participant level, the EEG dataset used in the first stage and the EEG dataset used in the second stage originated from the same participant. For the group-level, the EEG datasets used in the first stage were constructed by temporally concatenating each combination without repetition of the EEG datasets of five participants out of six, whereas the EEG dataset used in the second stage originated from the remaining participants. The average test classification results across datasets (mean ± S.D.) were 38.62 ± 8.36% for the single-participant, which was significantly higher than the chance level (12.50 ± 0.01%), and 27.26 ± 4.39% for the group-level which was also significantly higher than the chance level (12.49% ± 0.01%). The classification accuracy within [–45°, 45°] of the true direction is 70.03 ± 8.14% for single-participant and 62.63 ± 6.07% for group-level which may be promising for some real-life applications. Clustering and contribution analyses further revealed the brain regions involved in finger movement and the temporal aspect of their contribution to the classification. These results showed the possibility of using the ICA-based method in combination with other methods to build a real-time system to control prostheses.Keywords: brain-computer interface, electroencephalography, finger motion decoding, independent component analysis, pseudo real-time motion decoding
Procedia PDF Downloads 1371407 Plasma Selenium Concentration and Polymorphism of Selenoprotein and Prostate Cancer
Authors: Yu-Mei Hsueh, Cheng-Shiuan Tsai, Chao-Yuan Huang
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Prostate Cancer (PC) is a malignant tumor originated in prostate and is a second common male’s cancer in the world. Incidence of PC in Asia countries, have still been rising over the past few decades. As an antioxidant, selenium can slow down prostate cancer tumor progression, but the association between plasma selenium levels and risk of aggressive prostate cancer may be modified by different genotype of selenoprotein. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinaty total arsenic, and prostate cancer. Two hundred ninety five pathologically-confirmed cases of PC and 295 cancer-free controls were individually matched to case subjects by age (± 5 years) were recruited from Department of Urology of National Taiwan University Hospital, Taipei Municipal Wan Fang Hospital and Taipei Medical University Hospital. Personal interview and biospeciment of urine and blood collection from participants were conducted by well-trained interviewers after participants’ informed consent was obtained. Plasma selenium was measured by an inductively coupled plasma mass. Urinary arsenic concentration was detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of SEPP1rs3797310 and SEP15 rs5859 were determined using polymerase chain reaction-restriction fragment length polymorphism method. The higher plasma selenium was the lower OR of PC with a dose-response relationship. Prostate cancer patients with high plasma selenium had low tumor stage and grade. Participants carried SEPP1rs3797310 CT+TT genotype compared to those with CC genotype had a lower OR of PC in crude model; then this relationship was disappeared after confounder was adjusted. Prostate cancer patients with high urinary total arsenic concentration had high tumor stage and grade. Urinary total arsenic concentration was significantly positively related with plasma selenium and prostate specific antigen concentration. Participants with lower plasma selenium concentration and higher urinary total arsenic concentration compared to those with higher plasma selenium concentration and lower urinary total arsenic concentration had a higher OR of PC with a dose-response relationship.Keywords: prostate cancer, plasma selenium concentration, urinary arsenic concentration, prostate specific antigen
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