Search results for: Brain scan

Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: C. Román, M. Guevara, P. Salas, D. Duclap, J. Houenou, C. Poupon, J. F. Mangin, P. Guevara

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Diffusion Magnetic Resonance Imaging (dMRI) allows the non-invasive study of human brain white matter. From diffusion data, it is possible to reconstruct fiber trajectories using tractography algorithms. Our previous work consists in an automatic method for the identification of short association bundles of the superficial white matter (SWM), based on a whole brain inter-subject hierarchical clustering applied to a HARDI database. The method finds representative clusters of similar fibers, belonging to a group of subjects, according to a distance measure between fibers, using a non-linear registration (DTI-TK). The algorithm performs an automatic labeling based on the anatomy, defined by a cortex mesh parcelated with FreeSurfer software. The clustering was applied to two independent groups of 37 subjects. The clusters resulting from both groups were compared using a restrictive threshold of mean distance between each pair of bundles from different groups, in order to keep reproducible connections. In the left hemisphere, 48 reproducible bundles were found, while 43 bundles where found in the right hemisphere. An inter-hemispheric bundle correspondence was then applied. The symmetric horizontal reflection of the right bundles was calculated, in order to obtain the position of them in the left hemisphere. Next, the intersection between similar bundles was calculated. The pairs of bundles with a fiber intersection percentage higher than 50% were considered similar. The similar bundles between both hemispheres were fused and symmetrized. We obtained 30 common bundles between hemispheres. An atlas was created with the resulting bundles and used to segment 78 new subjects from another HARDI database, using a distance threshold between 6-8 mm according to the bundle length. Finally, a laterality index was calculated based on the bundle volume. Seven bundles of the atlas presented right laterality (IP_SP_1i, LO_LO_1i, Op_Tr_0i, PoC_PoC_0i, PoC_PreC_2i, PreC_SM_0i, y RoMF_RoMF_0i) and one presented left laterality (IP_SP_2i), there is no tendency of lateralization according to the brain region. Many factors can affect the results, like tractography artifacts, subject registration, and bundle segmentation. Further studies are necessary in order to establish the influence of these factors and evaluate SWM laterality.

Keywords: dMRI, hierarchical clustering, lateralization index, tractography

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Authors: A. Larrousi, M. Elkeurti, K. Amara, M. Zemouli, L. H. Coudert, I. R. Medvedev, F. C. De Lucia, Atsuko Maeda, R. W. C. McKellar, D. Appadoo

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Experimental and theoretical investigations of the microwave and far infrared spectra of CH3COD are reported. Two hundred twelve lines were identified in the far infrared spectrum recorded using the Canadian synchrotron radiation light source. Two thousand one hundred and sixty-eight lines in vt=0,1 and 216 in vt=2 have been measured in the microwave spectrum obtained using the fast scan submillimeter spectroscopic technique. A global analysis of the new data and of already available microwave lines has been carried out and yielded values for rotation–torsion parameters. The unitless weighted standard deviation of the fit is 1.6. 46 parameters and 216 lines were identified.

Keywords: CH3COD, torsion, the microwave spectra, far infrared spectra high resolution

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Authors: Chen-Chang Lee, Po-Chou Chen, Jo-Chi Jao, Chun-Chung Lui, Leung-Chit Tsang, Lain-Chyr Hwang

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Fetal Magnetic Resonance Imaging (MRI) is a challenge task because the fetal movements could cause motion artifact in MR images. The remedy to overcome this problem is to use fast scanning pulse sequences. The Single-Shot Fast Spin-Echo (SSFSE) T2-weighted imaging technique is routinely performed and often used as a gold standard in clinical examinations. Fast spoiled gradient-echo (FSPGR) T1-Weighted Imaging (T1WI) is often used to identify fat, calcification and hemorrhage. Fast Imaging Employing Steady-State Acquisition (FIESTA) is commonly used to identify fetal structures as well as the heart and vessels. The contrast of FIESTA image is related to T1/T2 and is different from that of SSFSE. The advantages and disadvantages of these two scanning sequences for fetal imaging have not been clearly demonstrated yet. This study aimed to compare these three rapid MRI techniques (SSFSE, FIESTA, and FSPGR) for fetal MRI examinations. The image qualities and influencing factors among these three techniques were explored. A 1.5T GE Discovery 450 clinical MR scanner with an eight-channel high-resolution abdominal coil was used in this study. Twenty-five pregnant women were recruited to enroll fetal MRI examination with SSFSE, FIESTA and FSPGR scanning. Multi-oriented and multi-slice images were acquired. Afterwards, MR images were interpreted and scored by two senior radiologists. The results showed that both SSFSE and T2W-FIESTA can provide good image quality among these three rapid imaging techniques. Vessel signals on FIESTA images are higher than those on SSFSE images. The Specific Absorption Rate (SAR) of FIESTA is lower than that of the others two techniques, but it is prone to cause banding artifacts. FSPGR-T1WI renders lower Signal-to-Noise Ratio (SNR) because it severely suffers from the impact of maternal and fetal movements. The scan times for these three scanning sequences were 25 sec (T2W-SSFSE), 20 sec (FIESTA) and 18 sec (FSPGR). In conclusion, all these three rapid MR scanning sequences can produce high contrast and high spatial resolution images. The scan time can be shortened by incorporating parallel imaging techniques so that the motion artifacts caused by fetal movements can be reduced. Having good understanding of the characteristics of these three rapid MRI techniques is helpful for technologists to obtain reproducible fetal anatomy images with high quality for prenatal diagnosis.

Keywords: fetal MRI, FIESTA, FSPGR, motion artifact, SSFSE

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Authors: Mustapha Majid

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Gone were the days when technicians/mechanics will have to spend too much time trying to identify a mechanical fault and rectify the problem. Now the emphasis is on the use of Automobile diagnosing Equipment through the use of computers and special software. An investigation conducted at Tamale Metropolis and Accra in the Northern and Greater Accra regions of Ghana, respectively. Methodology for data gathering were; questionnaires, physical observation, interviews, and newspaper. The study revealed that majority of mechanics lack computer skills which can enable them use diagnosis tools such as Exhaust Gas Analyzer, Scan Tools, Electronic Wheel Balancing machine, etc.

Keywords: diagnosing, local garages and modern garages, lack of knowledge of diagnosing posing an existential threat, training of local mechanics

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Authors: Mohamed Shafi Mahboob Ali

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Male breast cancer (MBC) is a rare entity with overall cases reported less than 1%. However, the incidence of MBC is regularly rising every year. Due to the lack of data on MBC, diagnosis and treatment are tailored to female breast cancer. MBC risk increases with age and is usually diagnosed ten years late as the disease progression is slow compared to female breast cancer (FBC). The most common feature of MBC is an intra-ductal variant, and often, upon diagnosis, the stage of the disease is already advanced. The Prognosis of MBC is often flawed, but new treatment modalities are emerging with the current knowledge and advancement. We presented a series of male breast cancer in our center, highlighting the clinicopathological, radiological and treatment options.

Keywords: male, breast, cancer, clinicopathology, ultrasound, CT scan

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Authors: Mohammad Hadi Mahmoodi, Soroor Zekrati

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The aim of this study was to investigate the relationship between hemispheric dominance and intonation learning of Iranian EFL students. In order to gain this goal, 52 female students from three levels of beginner, elementary and intermediate in Paradise Institute, and 18 male university students at Bu-Ali Sina University constituted the sample. In order to assist students learn the correct way of applying intonation to their everyday speech, the study proposed an interactive approach and provided students with visual aid through which they were able to see the intonation pattern on computer screen using 'Speech Analyzer' software. This software was also used to record subjects’ voice and compare them with the original intonation pattern. Edinburg Handedness Questionnaire (EHD), which ranges from –100 for strong left-handedness to +100 for strong right-handedness was used to indicate the hemispheric dominance of each student. The result of an independent sample t-test indicated that girls learned intonation pattern better than boys, and that right brained students significantly outperformed the left brained ones. Using one-way ANOVA, a significant difference between three proficiency levels was also found. The posthoc Scheffer test showed that the exact difference was between intermediate and elementary, and intermediate and beginner levels, but no significant difference was observed between elementary and beginner levels. The findings of the study might provide researchers with some helpful implications and useful directions for future investigation into the domain of the relationship between mind and second language learning.

Keywords: intonation, hemispheric dominance, visual aid, language learning, second language learning

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Authors: Chia-Yu Lin, Yu-Hsiang Shen, Cing-Ciao Ke, Chia-Hao Chang, Fan-Pin Tseng, Yu-Ching Ni, Sheng-Pin Tseng

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Tomosynthesis is an imaging system that generates a 3D image by scanning in a limited angular range. It could provide more depth information than traditional 2D X-ray single projection. Radiation dose in tomosynthesis is less than computed tomography (CT). Because of limited angular range scanning, there are many properties depending on scanning direction. Therefore, non-coplanar imaging technique was developed to improve image quality in traditional tomosynthesis. The purpose of this study was to establish the non-coplanar imaging technique of tomosynthesis system and evaluate this technique by the reconstructed image. INER prototype tomosynthesis system contains an X-ray tube, a flat panel detector, and a motion machine. This system could move X-ray tube in multiple directions during the acquisition. In this study, we investigated three different imaging techniques that were 2D X-ray single projection, traditional tomosynthesis, and non-coplanar tomosynthesis. An anthropopathic chest phantom was used to evaluate the image quality. It contained three different size lesions (3 mm, 5 mm and, 8 mm diameter). The traditional tomosynthesis acquired 61 projections over a 30 degrees angular range in one scanning direction. The non-coplanar tomosynthesis acquired 62 projections over 30 degrees angular range in two scanning directions. A 3D image was reconstructed by iterative image reconstruction algorithm (ML-EM). Our qualitative method was to evaluate artifacts in tomosynthesis reconstructed image. The quantitative method was used to calculate a peak-to-valley ratio (PVR) that means the intensity ratio of the lesion to the background. We used PVRs to evaluate the contrast of lesions. The qualitative results showed that in the reconstructed image of non-coplanar scanning, anatomic structures of chest and lesions could be identified clearly and no significant artifacts of scanning direction dependent could be discovered. In 2D X-ray single projection, anatomic structures overlapped and lesions could not be discovered. In traditional tomosynthesis image, anatomic structures and lesions could be identified clearly, but there were many artifacts of scanning direction dependent. The quantitative results of PVRs show that there were no significant differences between non-coplanar tomosynthesis and traditional tomosynthesis. The PVRs of the non-coplanar technique were slightly higher than traditional technique in 5 mm and 8 mm lesions. In non-coplanar tomosynthesis, artifacts of scanning direction dependent could be reduced and PVRs of lesions were not decreased. The reconstructed image was more isotropic uniformity in non-coplanar tomosynthesis than in traditional tomosynthesis. In the future, scan strategy and scan time will be the challenges of non-coplanar imaging technique.

Keywords: image reconstruction, non-coplanar imaging technique, tomosynthesis, X-ray imaging

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Authors: Yuko Ishiwaka, Tomohiro Yoshida, Tadateru Itoh

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Human makes preparation called readiness potential unconsciously (RP) before awareness of their own decision. For example, when recognizing a button and pressing the button, the RP peaks are observed 200 ms before the initiation of the movement. It has been known that the preparatory movements are acquired before actual movements, but it has not been still well understood how humans can obtain the RP during their growth. On the proposition of why the brain must respond earlier, we assume that humans have to adopt the dangerous environment to survive and then obtain the behavior to cover the various time lags distributed in the body. Without RP, humans cannot take action quickly to avoid dangerous situations. In taking action, the brain makes decisions, and signals are transmitted through the Spinal Cord to the muscles to the body moves according to the laws of physics. Our research focuses on the time lag of the neuron signal transmitting from a brain to muscle via a spinal cord. This time lag is one of the essential factors for readiness potential. We propose a firing pattern controller model of a motor nerve system considered innervation and jitter, which produces time lag. In our simulation, we adopt innervation and jitter in our proposed muscle-skeleton model, because these two factors can create infinitesimal time lag. Q10 Hodgkin Huxley model to calculate action potentials is also adopted because the refractory period produces a more significant time lag for continuous firing. Keeping constant power of muscle requires cooperation firing of motor neurons because a refractory period stifles the continuous firing of a neuron. One more factor in producing time lag is slow or fast-twitch. The Expanded Hill Type model is adopted to calculate power and time lag. We will simulate our model of muscle skeleton model by controlling the firing pattern and discuss the relationship between the time lag of physics and neurons. For our discussion, we analyze the time lag with our simulation for knee bending. The law of inertia caused the most influential time lag. The next most crucial time lag was the time to generate the action potential induced by innervation and jitter. In our simulation, the time lag at the beginning of the knee movement is 202ms to 203.5ms. It means that readiness potential should be prepared more than 200ms before decision making.

Keywords: firing patterns, innervation, jitter, motor nerve system, readiness potential

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Authors: Nitin Dwivedi, Jigna Shah

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Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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Authors: Vitor M. Vilas Boas, Cleison D. Silva, Gustavo S. Mafra, Alexandre Trofino Neto

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Motor imagery (MI) based brain-computer interfaces (BCI) uses event-related (de)synchronization (ERS/ ERD), typically recorded using electroencephalography (EEG), to translate brain electrical activity into control commands. To mitigate undesirable artifacts and noise measurements on EEG signals, methods based on band-pass filters defined by a specific frequency band (i.e., 8 – 30Hz), such as the Infinity Impulse Response (IIR) filters, are typically used. Spatial techniques, such as Common Spatial Patterns (CSP), are also used to estimate the variations of the filtered signal and extract features that define the imagined motion. The CSP effectiveness depends on the subject's discriminative frequency, and approaches based on the decomposition of the band of interest into sub-bands with smaller frequency ranges (SBCSP) have been suggested to EEG signals classification. However, despite providing good results, the SBCSP approach generally increases the computational cost of the filtering step in IM-based BCI systems. This paper proposes the use of the Fast Fourier Transform (FFT) algorithm in the IM-based BCI filtering stage that implements SBCSP. The goal is to apply the FFT algorithm to reduce the computational cost of the processing step of these systems and to make them more efficient without compromising classification accuracy. The proposal is based on the representation of EEG signals in a matrix of coefficients resulting from the frequency decomposition performed by the FFT, which is then submitted to the SBCSP process. The structure of the SBCSP contemplates dividing the band of interest, initially defined between 0 and 40Hz, into a set of 33 sub-bands spanning specific frequency bands which are processed in parallel each by a CSP filter and an LDA classifier. A Bayesian meta-classifier is then used to represent the LDA outputs of each sub-band as scores and organize them into a single vector, and then used as a training vector of an SVM global classifier. Initially, the public EEG data set IIa of the BCI Competition IV is used to validate the approach. The first contribution of the proposed method is that, in addition to being more compact, because it has a 68% smaller dimension than the original signal, the resulting FFT matrix maintains the signal information relevant to class discrimination. In addition, the results showed an average reduction of 31.6% in the computational cost in relation to the application of filtering methods based on IIR filters, suggesting FFT efficiency when applied in the filtering step. Finally, the frequency decomposition approach improves the overall system classification rate significantly compared to the commonly used filtering, going from 73.7% using IIR to 84.2% using FFT. The accuracy improvement above 10% and the computational cost reduction denote the potential of FFT in EEG signal filtering applied to the context of IM-based BCI implementing SBCSP. Tests with other data sets are currently being performed to reinforce such conclusions.

Keywords: brain-computer interfaces, fast Fourier transform algorithm, motor imagery, sub-band common spatial patterns

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Authors: Sai Snehitha Yadavalli, K. Sruthi, Swati Ghosh Acharyya

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Heavy metal ions are toxic to humans and all living species when exposed in large quantities or for long durations. Though Fe acts as a nutrient, when intake is in large quantities, it becomes toxic. These toxic heavy metal ions, when consumed through water, will cause many disorders and are harmful to all flora and fauna through biomagnification. Specifically, humans are prone to innumerable diseases ranging from skin to gastrointestinal, neurological, etc. In higher quantities, they even cause cancer in humans. Detection of these toxic heavy metal ions in water is thus important. Traditionally, the detection of heavy metal ions in water has been done by techniques like Inductively Coupled Plasma Mass Spectroscopy (ICPMS) and Atomic Absorption Spectroscopy (AAS). Though these methods offer accurate quantitative analysis, they require expensive equipment and cannot be used for on-site measurements. Anodic Stripping Voltammetry is a good alternative as the equipment is affordable, and measurements can be made at the river basins or lakes. In the current study, Square Wave Anodic Stripping Voltammetry (SWASV) was used to detect the heavy metal ions in water. Literature reports various electrodes on which deposition of heavy metal ions was carried out like Bismuth, Polymers, etc. The working electrode used in this study is a polyvinyl chloride (PVC) modified glassy carbon electrode (GCE). Ag/AgCl reference electrode and Platinum counter electrode were used. Biologic Potentiostat SP 300 was used for conducting the experiments. Through this work of simultaneous detection, four heavy metal ions were successfully detected at a time. The influence of modifying GCE with PVC was studied in comparison with unmodified GCE. The simultaneous detection of Cd⁺², Fe⁺², Co⁺², Pb⁺² heavy metal ions was done using PVC modified GCE by drop casting 1 wt.% of PVC dissolved in Tetra Hydro Furan (THF) solvent onto GCE. The concentration of all heavy metal ions was 0.2 mg/L, as shown in the figure. The scan rate was 0.1 V/s. Detection parameters like pH, scan rate, temperature, time of deposition, etc., were optimized. It was clearly understood that PVC helped in increasing the sensitivity and selectivity of detection as the current values are higher for PVC-modified GCE compared to unmodified GCE. The peaks were well defined when PVC-modified GCE was used.

Keywords: cadmium, cobalt, electrochemical sensing, glassy carbon electrodes, heavy metal Ions, Iron, lead, polyvinyl chloride, potentiostat, square wave anodic stripping voltammetry

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Authors: Anjali N. Shete, G. D. Mahajan, Nanda Somwanshi

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Context: Smartphones are the new generation of mobile phones; they have emerged over the last few years. Technology has developed so much that it has become part of our life and mobile phones are one of them. These smartphones are equipped with the capabilities to display photos, play games, watch videos and navigation, etc. The advances have a huge impact on many walks of life. The adoption of new technology has been challenging for the elderly. But, the elder population is also moving towards digitally connected lives. As age advances, there is a decline in the motor and cognitive functions of the brain, and hence the reaction time is affected. The study was undertaken to assess the usefulness of smartphones in improving cognitive functions. Aims and Objectives: The aim of the study was to observe the effects of smartphone addiction on reaction time in elderly population Material and Methods: This is an experimental study. 100 elderly subjects were enrolled in this study randomly from urban areas. They all were using smartphones for several hours a day. They were divided into two groups according to the scores of the mobile phone addiction scale (MPAS). Simple reaction time was estimated by the Ruler drop method. The reaction time was then calculated for each subject in both groups. The data were analyzed using mean, standard deviation, and Pearson correlation test. Results: The mean reaction time in Group A is 0.27+ 0.040 and in Group B is 0.20 + 0.032. The values show a statistically significant change in reaction time. Conclusion: Group A with a high MPAS score has a low reaction time compared to Group B with a low MPAS score. Hence, it can be concluded that the use of smartphones in the elderly is useful, delaying the neurological decline, and smarten the brain.

Keywords: smartphones, MPAS, reaction time, elderly population

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Authors: Zeena Dcosta, Junaid Ahmed, Ceena Denny, Nandita Shenoy

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In the field of dentistry, there are many conditions which warrant the requirement of three-dimensional imaging that can aid in diagnosis and therapeutic management. Cone beam computed tomography (CBCT) is considered highly accurate in producing a three-dimensional image of an object and provides a complete insight of various findings in the captured volume. But, most of the clinicians focus primarily on the teeth and jaws and numerous unanticipated clinically significant incidental findings may be missed out. Rapid integration of CBCT into the practice of dentistry has led to the detection of various incidental findings. However, the prevalence of these incidental findings is still unknown. Thus, the study aimed to discern the reason for referral and to identify incidental findings on the referred CBCT scans. Patient’s demographic data such as age and gender was noted. CBCT scans of multiple fields of views (FOV) were considered. The referral for CBCT scans was broadly classified into two major categories: diagnostic scan and treatment planning scan. Any finding on the CBCT volumes, other than the area of concern was recorded as incidental finding which was noted under airway, developmental, pathological, endodontics, TMJ, bone, soft tissue calcifications and others. Few of the incidental findings noted under airway were deviated nasal septum, nasal turbinate hypertrophy, mucosal thickening and pneumatization of sinus. Developmental incidental findings included dilaceration, impaction, pulp stone and gubernacular canal. Resorption of teeth and periapical pathologies were noted under pathological incidental findings. Root fracture along with over and under obturation was noted under endodontics. Incidental findings under TMJ were flattening, erosion and bifid condyle. Enostosis and exostosis were noted under bone lesions. Tonsillolth, sialolith and calcified styloid ligament were noted under soft tissue calcifications. Incidental findings under others included foreign body, fused C1- C2 vertebrae, nutrient canals, and pneumatocyst. Maxillofacial radiologists should be aware of possible incidental findings and should be vigilant about comprehensively evaluating the entire captured volume, which can help in early diagnosis of any potential pathologies that may go undetected. Interpretation of CBCT is truly an art and with the experience, we can unravel the secrets hidden in the grey shades of the radiographic image.

Keywords: cone beam computed tomography, incidental findings, maxillofacial region, radiologist

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Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

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Authors: Keyvan Kashkouli Nejad, Motoaki Sugiura, Atsushi Sato, Takayuki Nozawa, Hyeonjeong Jeong, Sugiko Hanawa , Yuka Kotozaki, Ryuta Kawashima

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The perception of agency/control is altered with presence of discrepancies in the environment or mismatch of predictions (of possible results) and actual results the sense of agency might become altered. Synofzik et al. proposed a two layer model of agency: In the first layer, the Feeling of Agency (FoA) is not directly available to awareness; a slight mismatch in the environment/outcome might cause alterations in FoA, while the agent still feels in control. If the discrepancy passes a threshold, it becomes available to consciousness and alters Judgment of Agency (JoA), which is directly available in the person’s awareness. Most experiments so far only investigate subjects rather conscious JoA, while FoA has been neglected. In this experiment we target FoA by using subliminal discrepancies that can not be consciously detectable by the subjects. Here, we explore whether we can detect this two level model in the subjects behavior and then try to map this in their brain activity. To do this, in a fMRI study, we incorporated both consciously detectable mismatching between action and result and also subliminal discrepancies in the environment. Also, unlike previous experiments where subjective questions from the participants mainly trigger the rather conscious JoA, we also tried to measure the rather implicit FoA by asking participants to rate their performance. We compared behavioral results and also brain activation when there were conscious discrepancies and when there were subliminal discrepancies against trials with no discrepancies and against each other. In line with our expectations, conditions with consciously detectable incongruencies triggered lower JoA ratings than conditions without. Also, conditions with any type of discrepancies had lower FoA ratings compared to conditions without. Additionally, we found out that TPJ and angular gyrus in particular to have a role in coding of JoA and also FoA.

Keywords: agency, fMRI, TPJ, two layer model

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Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili

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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.

Keywords: arsenic, manganese, behavior, learning, neuron

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Authors: Ramandeep Kaur, Gurjit Singh Bhathal

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Cancer diagnosis is very difficult task. Magnetic resonance imaging (MRI) scan is used to produce image of any part of the body and provides an efficient way for diagnosis of cancer or tumor. In existing method, fuzzy clustering mean (FCM) is used for the diagnosis of the tumor. In the proposed method FCM is used to diagnose the cancer of the foot. FCM finds the centroids of the clusters of the foot cancer obtained from MRI images. FCM thresholding result shows the extract region of the cancer. Morphological operations are applied to get extracted region of cancer.

Keywords: magnetic resonance imaging (MRI), fuzzy C mean clustering, segmentation, morphological operations

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Authors: M. Saard, A. Kolk, K. Sepp, L. Pertens, L. Reinart, C. Kööp

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Introduction: Social competence is often impaired in children with acquired brain injury (ABI), but evidence-based rehabilitation for social skills has remained undeveloped. Modern technology-based methods create effective and safe learning environments for pediatric social skills remediation. The aim of the study was to implement our structured model of neuro rehab for socio-cognitive deficit using multitouch-multiuser tabletop (MMT) computer-based platforms and virtual reality (VR) technology. Methods: 40 children aged 8-13 years (yrs) have participated in the pilot study: 30 with ABI -epilepsy, traumatic brain injury and/or tic disorder- and 10 healthy age-matched controls. From the patients, 12 have completed the training (M = 11.10 yrs, SD = 1.543) and 20 are still in training or in the waiting-list group (M = 10.69 yrs, SD = 1.704). All children performed the first individual and paired assessments. For patients, second evaluations were performed after the intervention period. Two interactive applications were implemented into rehabilitation design: Snowflake software on MMT tabletop and NoProblem on DiamondTouch Table (DTT), which allowed paired training (2 children at once). Also, in individual training sessions, HTC Vive VR device was used with VR metaphors of difficult social situations to treat social anxiety and train social skills. Results: At baseline (B) evaluations, patients had higher deficits in executive functions on the BRIEF parents’ questionnaire (M = 117, SD = 23.594) compared to healthy controls (M = 22, SD = 18.385). The most impaired components of social competence were emotion recognition, Theory of Mind skills (ToM), cooperation, verbal/non-verbal communication, and pragmatics (Friendship Observation Scale scores only 25-50% out of 100% for patients). In Sentence Completion Task and Spence Anxiety Scale, the patients reported a lack of friends, behavioral problems, bullying in school, and social anxiety. Outcome evaluations: Snowflake on MMT improved executive and cooperation skills and DTT developed communication skills, metacognitive skills, and coping. VR, video modelling and role-plays improved social attention, emotional attitude, gestural behaviors, and decreased social anxiety. NEPSY-II showed improvement in Affect Recognition [B = 7, SD = 5.01 vs outcome (O) = 10, SD = 5.85], Verbal ToM (B = 8, SD = 3.06 vs O = 10, SD = 4.08), Contextual ToM (B = 8, SD = 3.15 vs O = 11, SD = 2.87). ToM Stories test showed an improved understanding of Intentional Lying (B = 7, SD = 2.20 vs O = 10, SD = 0.50), and Sarcasm (B=6, SD = 2.20 vs O = 7, SD = 2.50). Conclusion: Neurorehabilitation based on the Structured Model of Neurorehab for Socio-Cognitive Deficit in children with ABI were effective in social skills remediation. The model helps to understand theoretical connections between components of social competence and modern interactive computerized platforms. We encourage therapists to implement these next-generation devices into the rehabilitation process as MMT and VR interfaces are motivating for children, thus ensuring good compliance. Improving children’s social skills is important for their and their families’ quality of life and social capital.

Keywords: acquired brain injury, children, social skills deficit, technology-based neurorehabilitation

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Authors: Salina Budin, Shaira Ismail

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Students learn effectively in a learning environment with a suitable teaching approach that matches their learning preferences. The main objective of the study is to examine the learning preferences amongst the students in the Science and Technology (S&T), and Social Science (SS) fields of study at the Universiti Teknologi Mara (UiTM), Pulau Pinang. The measurement instrument is based on the Dunn and Dunn Learning Styles which measure five elements of learning styles; environmental, sociological, emotional, physiological and psychological. Questionnaires are distributed amongst undergraduates in the Faculty of Mechanical Engineering and Faculty of Business Management. The respondents comprise of 131 diploma students of the Faculty of Mechanical Engineering and 111 degree students of the Faculty of Business Management. The results indicate that, both S&T and SS students share a similar learning preferences on the environmental aspect, emotional preferences, motivational level, learning responsibility, persistent level in learning and learning structure. Most of the S&T students are concluded as analytical learners and the majority of SS students are global learners. Both S&T and SS students are concluded as visual learners, preferred to be in an active mobility in a relaxing and enjoying mode with some light of refreshments during the learning process and exhibited reflective characteristics in learning. Obviously, the S&T students are considered as left brain dominant, whereas the SS students are right brain dominant. The findings highlighted that both categories of students exhibited similar learning preferences except on psychological preferences.

Keywords: learning preferences, Dunn and Dunn learning style, teaching approach, science and technology, social science

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Authors: Yousif Mohamed Y. Abdallah, Khalid H. Eltom

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This is an experimental study deals with measurement of the periodic physiological organ motion during lung external irradiation in order to reduce the exposure of healthy tissue during radiation treatments. The results showed for left lung displacement reading (4.52+1.99 mm) and right lung is (8.21+3.77 mm) which the radiotherapy physician should take suitable countermeasures in case of significant errors. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, the calculation of tumour mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a high resolution CT scan with a margin of 3-5 mm is appropriate.

Keywords: physiological motion, lung, external irradiation, radiation medicine

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Authors: M. G. Talasbayen, N. N. Dyussenbayev, Y. D. Kali, R. A. Zholbarysov, Y. N. Duissenbayev, I. Z. Mammadinova, S. M. Nuradilov

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Background. Hemorrhagic stroke is an acute cerebrovascular accident resulting from rupture of a cerebral vessel or increased permeability of the wall and imbibition of blood into the brain parenchyma. Arterial hypertension is a common cause of hemorrhagic stroke. Male gender and age over 55 years is a risk factor for intracerebral hemorrhage. Treatment of intracerebral hemorrhage is aimed at the primary pathophysiological link: the relief of coagulopathy and the control of arterial hypertension. Early surgical treatment can limit cerebral compression; prevent toxic effects of blood to the brain parenchyma. Despite progress in the development of neuroimaging data, the use of minimally invasive techniques, and navigation system, mortality from intracerebral hemorrhage remains high. Materials and methods. The study included 78 patients (62.82% male and 37.18% female) with a verified diagnosis of hemorrhagic stroke in the period from 2019 to 2021. The age of patients ranged from 25 to 80 years, the average age was 54.66±11.9 years. Demographic, brain CT data (localization, volume of hematomas), methods of treatment, and disease outcome were analyzed. Results. The retrospective analyze demonstrate that 78.2% of all patients underwent surgical treatment: decompressive craniectomy in 37.7%, craniotomy with hematoma evacuation in 29.5%, and hematoma draining in 24.59% cases. The study of the proportion of deaths, depending on the volume of intracerebral hemorrhage, shows that the number of deaths was higher in the group with a hematoma volume of more than 60 ml. Evaluation of the relationship between the time before surgery and mortality demonstrates that the most favorable outcome is observed during surgical treatment in the interval from 3 to 24 hours. Mortality depending on age did not reveal a significant difference between age groups. An analysis of the impact of the surgery type on mortality reveals that decompressive craniectomy with or without hematoma evacuation led to an unfavorable outcome in 73.9% of cases, while craniotomy with hematoma evacuation and drainage led to mortality only in 28.82% cases. Conclusion. Even though the multimodal approaches, the development of surgical techniques and equipment, and the selection of optimal conservative therapy, the question of determining the tactics of managing and treating hemorrhagic strokes is still controversial. Nevertheless, our experience shows that surgical intervention within 24 hours from the moment of admission and craniotomy with hematoma evacuation improves the prognosis of treatment outcomes.

Keywords: hemorragic stroke, Intracerebral hemorrhage, surgical treatment, stroke mortality

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Evangelos Koumparoudis

Abstract:

The definition of death is a deep philosophical question, and no single meaning can be ascribed to it. This essay focuses on the ontological, epistemological, and ethical aspects of death and dying in view of technological progress in information technology and biomedicine. It starts with the ad hoc 1968 Harvard committee that proposed that the criterion for the definition of death be irreversible coma and then refers to the debate over the whole brain death formula, emphasizing the integrated function of the organism and higher brain formula, taking consciousness and personality as essential human characteristics. It follows with the contribution of information technology in personalized and precision medicine and anti-aging measures aimed at life prolongation. It also touches on the possibility of the creation of human-machine hybrids and how this raises ontological and ethical issues that concern the “cyborgization” of human beings and the conception of the organism and personhood based on a post/transhumanist essence, and, furthermore, if sentient AI capable of autonomous decision-making that might even surpass human intelligence (singularity, superintelligence) deserves moral or legal personhood. Finally, there is the question as to whether death and dying should be redefined at a transcendent level, which is reinforced by already-existing technologies of “virtual after-” life and the possibility of uploading human minds. In the last section, I refer to the current (and future) applications of nanomedicine in diagnostics, therapeutics, implants, and tissue engineering as well as the aspiration to “immortality” by cryonics. The definition of death is reformulated since age and disease elimination may be realized, and the criterion of irreversibility may be challenged.

Keywords: death, posthumanism, infomedicine, nanomedicine, cryonics

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Authors: Nabi Ullah

Abstract:

The single-step solvothermal method is used to prepare Cu/CuSe as an electrocatalyst for methanol electro-oxidation reaction (MOR). 1,3-butane-diol is selected as a reaction medium, whose viscosity and complex formation with Cu(II) ions dictate the catalyst morphology. The catalyst has a macroporous structure, which is composed of nanoballs with a high purity, crystallinity, and uniform morphology. The electrocatalyst is excellent for MOR, as it delivers a current density of 37.28 mA/mg at a potential of 0.6 V (vs Ag/AgCl) in the electrolyte of 1 M KOH and 0.75 M methanol at a 50 mV/s scan rate under conditions of cyclic voltammetry. The catalyst also shows good stability for 3600 s with negligible charge transfer resistance and a high electrochemical active surface area (ECSA) value of 0.100 mF/cm².

Keywords: MOR, copper selenide, electocatalyst, energy application

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Authors: Takashi Kaburagi, Masashi Takenaka, Yosuke Kurihara, Takashi Matsumoto

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Major depressive disorder (MDD) is one of the most common mental illnesses today. It is believed to be caused by a combination of several factors, including stress. Stress can be quantitatively evaluated using the State-Trait Anxiety Inventory (STAI), one of the best indices to evaluate anxiety. Although STAI scores are widely used in applications ranging from clinical diagnosis to basic research, the scores are calculated based on a self-reported questionnaire. An objective evaluation is required because the subject may intentionally change his/her answers if multiple tests are carried out. In this article, we present a modified index called the “multi-channel Laterality Index at Rest (mc-LIR)” by recording the brain activity from a wider area of the frontal lobe using multi-channel functional near-infrared spectroscopy (fNIRS). The presented index aims to measure multiple positions near the F_pz defined by the international 10-20 system positioning. Using 24 subjects, the dependencies on the number of measuring points used to calculate the mc-LIR and its correlation coefficients with the STAI scores are reported. Furthermore, a simple linear regression was performed to estimate the STAI scores from mc-LIR. The cross-validation error is also reported. The experimental results show that using multiple positions near the Fpz will improve the correlation coefficients and estimation than those using only two positions.

Keywords: frontal lobe, functional near-infrared spectroscopy, state-trait anxiety inventory score, stress

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Authors: Zerihun Ketema Tadesse, Dabbu Suman Reddy

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Brain-Computer Interfaces (BCIs) give the possibility for disabled people to communicate and control devices. This work aims at developing steady-state visual evoked potential (SSVEP)-based BCI for patients with limb disabilities. In hospitals, devices like nurse emergency call devices, lights, and TV sets are what patients use most frequently, but these devices are operated manually or using the remote control. Thus, disabled patients are not able to operate these devices by themselves. Hence, SSVEP-based BCI system that can allow disabled patients to control nurse calling device and other devices is proposed in this work. Portable LED visual stimulator that flickers at specific frequencies of 7Hz, 8Hz, 9Hz and 10Hz were developed as part of this project. Disabled patients can stare at specific flickering LED of visual stimulator and Emotiv EPOC used to acquire EEG signal in a non-invasive way. The acquired EEG signal can be processed to generate various control signals depending upon the amplitude and duration of signal components. MATLAB software is used for signal processing and analysis and also for command generation. Arduino is used as a hardware interface device to receive and transmit command signals to the experimental setup. Therefore, this study is focused on the design and development of Steady-state visually evoked potential (SSVEP)-based BCI for limb disabled patients, which helps them to operate and control devices in the hospital room/wards.

Keywords: SSVEP-BCI, Limb Disabled Patients, LED Visual Stimulator, EEG signal, control devices, hospital room/wards

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Authors: Umedov Mekhroz, Griaznova Svetlana

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In connection with the growth of oncological diseases, the design of centers for diagnostics and the production of radiopharmaceuticals is the most relevant area of healthcare facilities. The design of new nuclear medicine centers should be carried out from the standpoint of solving the following tasks: the availability of medical care, functionality, environmental friendliness, sustainable development, improving the safety of drugs, the use of which requires special care, reducing the rate of environmental pollution, ensuring comfortable conditions for the internal microclimate, adaptability. The purpose of this article is to substantiate architectural and planning solutions, formulate recommendations and principles for the design of nuclear medicine centers and determine the connections between the production and medical functions of a building. The advantages of combining the production of radiopharmaceuticals and the department of medical care: less radiation activity is accumulated, the cost of the final product is lower, and there is no need to hire a transport company with a special license for transportation. A medical imaging department is a structural unit of a medical institution in which diagnostic procedures are carried out in order to gain an idea of the internal structure of various organs of the body for clinical analysis. Depending on the needs of a particular institution, the department may include various rooms that provide medical imaging using radiography, ultrasound diagnostics, and the phenomenon of nuclear magnetic resonance. The production of radiopharmaceuticals is an object intended for the production of a pharmaceutical substance containing a radionuclide and intended for introduction into the human body or laboratory animal for the purpose of diagnosis, evaluation of the effectiveness of treatment, or for biomedical research. The research methodology includes the following subjects: study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research; An integrated approach to the study of existing international experience of PET / CT scan centers and the production of radiopharmaceuticals; Elaboration of graphical analysis and diagrams based on the system analysis of the processed information; Identification of methods and principles of functional zoning of nuclear medicine centers. The result of the research is the identification of the design principles of nuclear medicine centers with the functions of the production of radiopharmaceuticals and the department of medical imaging. This research will be applied to the design and construction of healthcare facilities in the field of nuclear medicine.

Keywords: architectural planning solutions, functional zoning, nuclear medicine, PET/CT scan, production of radiopharmaceuticals, radiotherapy

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Authors: Abdulrahman Algaeed

Abstract:

The Ophthalmic Ultrasound is the easiest method of early diagnosing Retinoblastoma after clinical examination. It can be done with ease without sedation. King Khaled Eye Specialist Hospital is a tertiary care center where Retinoblastoma patients are often seen and treated there. The first modality to rule out the disease is Ophthalmic Ultrasound. Classic Retinoblastoma is easily diagnosed by using the conventional 10MHz Ophthalmic Ultrasound probe in the regular clinic setup. Retinal lesion with multiple, very highly reflective surfaces within lesion typical of Calcium deposits. The use of Standardized A-scan is very useful where internal reflectivity is classified as very highly reflective. Color Doppler is extremely useful as well to show the blood flow within lesion/s. In conclusion: Ophthalmic Ultrasound should be the first tool to be used to diagnose Retinoblastoma after clinical examination. The accuracy of the Exam is very high.

Keywords: doppler, retinoblastoma, reflectivity, ultrasound

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Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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