Search results for: brain injury

Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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Authors: Yang Xinyu, GongCong, Hu Changjuan

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Stairway spaces are a crucial component of the pathway systems and vertical transportation networks in mountain city parks. These spaces are closely integrated with the undulating terrain of mountain environments, resulting in continuously changing spatial conditions that can significantly influence participants' behavioral characteristics, thereby affecting their perception. EEG signals, which have been proven to reflect various non-attentive physiological activities in the brain, are widely used in studies related to stress recovery effects and emotional perception. Existing research predominantly examines the impact of spatial characteristics and landscape elements of trails and greenways in plain cities on participants' perception, utilizing EEG signals in laboratory-simulated environments. These studies have preliminarily revealed the relationship between spatial environments and perception preferences. However, on-site ergonomics research in mountain environments remains relatively underdeveloped. To address this gap, the Stairway spaces in Pipashan Park, Chongqing, were selected as the research object. Wearable hydrogel EEG devices were employed to monitor participants' EEG data in real environments, and a Generalized Linear Mixed Model (GLMM) was constructed to explore differences in participants' perception under different paths and modes of movement, as well as the impact of visual and auditory environmental elements within each path on their perception. The model analysis results indicate significant differences in EEG data across different paths and movement modes. Additionally, typical mountainous spatial characteristics, such as openness, green view index, and elevation difference, are identified as key factors influencing participants' EEG data. Higher levels of natural sound and green view index were shown to effectively alleviate participants' stress perception in mountain stairway spaces. The findings reveal the intrinsic connections between environment, behavior, and perception in stairway spaces of mountain city parks, providing a theoretical basis for optimizing the design of stairway spaces in mountain cities.

Keywords: audio-visual perception, EEG monitoring, mountain city park, real environment, stairway space

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Authors: Diego Abbo

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On February 15, 2012 off the Indian coast of Kerala, in position 091702N-0760180E by the oil tanker Enrica Lexie, flying the Italian flag, bursts of 5.56 x45 caliber shots were fired from assault rifles AR/70 Italian-made Beretta towards the Indian fisher boat St. Anthony. The shots that hit the St. Anthony fishing boat were six, of which two killed the Indian fishermen Ajesh Pink and Valentine Jelestine. From the analysis concerning the kinematic engagement of the two ships and from the autopsy and ballistic results of the Indian judicial authorities it is possible to reconstruct the trajectories of the six aforementioned shots. This essay reconstructs the trajectories of the six shots that cannot be of direct shooting but have undergone a rebound on the water. The investigation carried out scientifically demonstrates the rebound of the blows on the water, the gyrostatic deviation due to the rebound and the tumbling effect always due to the rebound as regards intermediate ballistics. In consideration of the four shots that directly impacted the fishing vessel, the current examination proves, with scientific value, that the trajectories could not be downwards but upwards. Also, the trajectory of two shots that hit to death the two fishermen could not be downwards but only upwards. In fact, this paper demonstrates, with scientific value: The loss of speed of the projectiles due to the rebound on the water; The tumbling effect in the ballistic medium within the two victims; The permanent cavities subject to the injury ballistics and the related ballistic trauma that prevented homeostasis causing bleeding in one case; The thermo-hardening deformation of the bullet found in Valentine Jelestine's skull; The upward and non-downward trajectories. The paper constitutes a tool in forensic ballistics in that it manages to reconstruct, from the final spot of the projectiles fired, all phases of ballistics like the internal one of the weapons that fired, the intermediate one, the terminal one and the penetrative structural one. In general terms the ballistics reconstruction is based on measurable parameters whose entity is contained with certainty within a lower and upper limit. Therefore, quantities that refer to angles, speed, impact energy and firing position of the shooter can be identified within the aforementioned limits. Finally, the investigation into the internal bullet track, obtained from any autopsy examination, offers a significant “lesson learned” but overall a starting point to contain or mitigate bleeding as a rescue from future gunshot wounds.

Keywords: impact physics, intermediate ballistics, terminal ballistics, tumbling effect

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Authors: Sruthi Raveendran

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Developmental dyslexia, characterized by reading difficulties despite normal intelligence, presents a significant challenge for bilingual children navigating languages with varying degrees of orthographic transparency. This study bridges a critical gap in dyslexia interventions for bilingual populations in India by examining how consistency and predictability of letter-sound relationships in a writing system (orthographic transparency) influence the ability to understand and manipulate the building blocks of sound in language (phonological processing). The study employed a computerized visual rhyme-judgment task with concurrent EEG (electroencephalogram) recording. The task compared reaction times, accuracy of performance, and event-related potential (ERP) components (N170, N400, and LPC) for rhyming and non-rhyming stimuli in two orthographies: English (opaque orthography) and Kannada (transparent orthography). As hypothesized, the results revealed advantages in phonological processing tasks for transparent orthography (Kannada). Children with dyslexia were faster and more accurate when judging rhymes in Kannada compared to English. This suggests that a language with consistent letter-sound relationships (transparent orthography) facilitates processing, especially for tasks that involve manipulating sounds within words (rhyming). Furthermore, brain activity measured by event-related potentials (ERP) showed less effort required for processing words in Kannada, as reflected by smaller N170, N400, and LPC amplitudes. These findings highlight the crucial role of orthographic transparency in optimizing reading performance for bilingual children with dyslexia. These findings emphasize the need for language-specific intervention strategies that consider the unique linguistic characteristics of each language. While acknowledging the complexity of factors influencing dyslexia, this research contributes valuable insights into the impact of orthographic transparency on phonological awareness in bilingual children. This knowledge paves the way for developing tailored interventions that promote linguistic inclusivity and optimize literacy outcomes for children with dyslexia.

Keywords: developmental dyslexia, phonological awareness, rhyme judgment, orthographic transparency, Kannada, English, N170, N400, LPC

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Authors: Amy Pullen, Samantha Rodrigues, David Kieser, Brian Shaw

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The aim of the study was to determine if a projectile interacting with the lungs increases the severity of injury in comparison to a projectile interacting with the ribs or intercostal muscle. This comparative study employed a 10% gelatine based model with either porcine ribs or balloons embedded to represent a lung. Four sample groups containing five samples were evaluated; these were control (plain gel), intercostal impact, rib impact, and lung impact. Two ammunition natures were evaluated at a range of 10m; these were 5.56x45mm and 7.62x51mm. Aspects of projectile behavior were quantified including exiting projectile weight, location of yawing, projectile fragmentation and distribution, location and area of the temporary cavity, permanent cavity formation, and overall energy deposition. Major findings included the cavity showing a higher percentage of the projectile weight exit the block than the intercostal and ribs, but similar to the control for the 5.56mm ammunition. However, for the 7.62mm ammunition, the lung was shown to have a higher percentage of the projectile weight exit the block than the control, intercostal and ribs. The total weight of projectile fragments as a function of penetration depth revealed large fluctuations and significant intra-group variation for both ammunition natures. Despite the lack of a clear trend, both plots show that the lung leads to greater projectile fragments exiting the model. The lung was shown to have a later center of the temporary cavity than the control, intercostal and ribs for both ammunition types. It was also shown to have a similar temporary cavity volume to the control, intercostal and ribs for the 5.56mm ammunition and a similar temporary cavity to the intercostal for the 7.62mm ammunition The lung was shown to leave a similar projectile tract than the control, intercostal and ribs for both ammunition types. It was also shown to have larger shear planes than the control and the intercostal, but similar to the ribs for the 5.56mm ammunition, whereas it was shown to have smaller shear planes than the control but similar shear planes to the intercostal and ribs for the 7.62mm ammunition. The lung was shown to have less energy deposited than the control, intercostal and ribs for both ammunition types. This comparative study provides insights into the influence of the lungs on thoracic gunshot trauma. It indicates that the lungs limits projectile deformation and causes a later onset of yawing and subsequently limits the energy deposited along the wound tract creating a deeper and smaller cavity. This suggests that lung impact creates an altered pattern of local energy deposition within the target which will affect the severity of trauma.

Keywords: ballistics, lung, trauma, wounding

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Authors: Man-Yun Liu, Emily Chia-Yu Su

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Alzheimer's disease (AD) is the public health crisis of the 21st century. AD is a degenerative brain disease and the most common cause of dementia, a costly disease on the healthcare system. Unfortunately, the cause of AD is poorly understood, furthermore; the treatments of AD so far can only alleviate symptoms rather cure or stop the progress of the disease. Currently, there are several ways to diagnose AD; medical imaging can be used to distinguish between AD, other dementias, and early onset AD, and cerebrospinal fluid (CSF). Compared with other diagnostic tools, blood (plasma) test has advantages as an approach to population-based disease screening because it is simpler, less invasive also cost effective. In our study, we used blood biomarkers dataset of The Alzheimer’s disease Neuroimaging Initiative (ADNI) which was funded by National Institutes of Health (NIH) to do data analysis and develop a prediction model. We used independent analysis of datasets to identify plasma protein biomarkers predicting early onset AD. Firstly, to compare the basic demographic statistics between the cohorts, we used SAS Enterprise Guide to do data preprocessing and statistical analysis. Secondly, we used logistic regression, neural network, decision tree to validate biomarkers by SAS Enterprise Miner. This study generated data from ADNI, contained 146 blood biomarkers from 566 participants. Participants include cognitive normal (healthy), mild cognitive impairment (MCI), and patient suffered Alzheimer’s disease (AD). Participants’ samples were separated into two groups, healthy and MCI, healthy and AD, respectively. We used the two groups to compare important biomarkers of AD and MCI. In preprocessing, we used a t-test to filter 41/47 features between the two groups (healthy and AD, healthy and MCI) before using machine learning algorithms. Then we have built model with 4 machine learning methods, the best AUC of two groups separately are 0.991/0.709. We want to stress the importance that the simple, less invasive, common blood (plasma) test may also early diagnose AD. As our opinion, the result will provide evidence that blood-based biomarkers might be an alternative diagnostics tool before further examination with CSF and medical imaging. A comprehensive study on the differences in blood-based biomarkers between AD patients and healthy subjects is warranted. Early detection of AD progression will allow physicians the opportunity for early intervention and treatment.

Keywords: Alzheimer's disease, blood-based biomarkers, diagnostics, early detection, machine learning

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Authors: Deeba N. Baig, Ateeqa Ijaz, Saloome Rafiq

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Camel is a religious and culturally significant animal in Asian and African regions. In Pakistan Dromedary and Bactrian are common camel breeds. Other than the transportation use, it is a pivotal source of milk and meat. The quality of its milk and meat is predominantly dependent on the geographical location and variety of vegetation available for the diet. Camel milk (CM) is highly nutritious because of its reduced cholesterol and sugar contents along with enhanced minerals and vitamins level. The absence of beta-lactoglobulin (like human milk), makes CM a safer alternative for infants and children having Cow Milk Allergy (CMA). In addition to this, it has a unique probiotic profile both in raw and fermented form. Number of Lactic acid bacteria (LAB) including lactococcus, lactobacillus, enterococcus, streptococcus, weissella, pediococcus and many other bacteria have been detected. From these LAB Lactobacilli, Bifidobacterium and Enterococcus are widely used commercially for fermentation purpose. CM has high therapeutic value as its effectiveness is known against various ailments like fever, arthritis, asthma, gastritis, hepatitis, Jaundice, constipation, postpartum care of women, anti-venom, dropsy etc. It also has anti-diabetic, anti-microbial, antitumor potential along with its robust efficacy in the treatment of auto-immune disorders. Recently, the role of CM has been explored in brain-gut axis for the therapeutics of neurodevelopmental disorders. In this connection, a lot of grey area was available to explore the probiotics and therapeutics latent in the CM available in Pakistan. Thus, current study was designed to explore the predominant probiotic flora and antimicrobial potential of CM from different local breeds of Pakistan. The probiotics have been identified through biochemical, physiological and ribo-typing methods. In addition to this, bacteriocins (antimicrobial-agents) were screened through PCR-based approach. Results of this study revealed that CM from different breeds of camel depicted a number of similar probiotic candidates along with the range of limited variability. However, the nucleotide sequence analysis of selected anti-listerial bacteriocins exposed least variability. As a conclusion, the CM has sufficient probiotic availability and significant anti-microbial potential.

Keywords: bacteriocins, camel milk, probiotics potential, therapeutics

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Authors: A. Schander, T. Tessmann, H. Stemmann, S. Strokov, A. Kreiter, W. Lang

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For the chronic application of neural prostheses and other brain-computer interfaces, long-term stable microelectrodes for electrical stimulation are essential. In recent years many developments were done to investigate different appropriate materials for these electrodes. One of these materials is the electrical conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT), which has lower impedance and higher charge injection capacity compared to noble metals like gold and platinum. However the long-term stability of this polymer is still unclear. Thus this paper reports on the in-vitro evaluation of the long-term stability of PEDOT coated gold microelectrodes. For this purpose a highly flexible electrocorticography (ECoG) electrode array, based on the polymer polyimide, is used. This array consists of circular gold electrodes with a diameter of 560 µm (0.25 mm2). In total 25 electrodes of this array were coated simultaneously with the polymer PEDOT:PSS in a cleanroom environment using a galvanostatic electropolymerization process. After the coating the array is additionally sterilized using a steam sterilization process (121°C, 1 bar, 20.5 min) to simulate autoclaving prior to the implantation of such an electrode array. The long-term measurements were performed in phosphate-buffered saline solution (PBS, pH 7.4) at the constant body temperature of 37°C. For the in-vitro electrical stimulation a one channel bipolar current stimulator is used. The stimulation protocol consists of a bipolar current amplitude of 5 mA (cathodal phase first), a pulse duration of 100 µs per phase, a pulse pause of 50 µs and a frequency of 1 kHz. A PEDOT:PSS coated gold electrode with an area of 1 cm2 serves as the counter electrode. The electrical stimulation is performed continuously with a total amount of 86.4 million bipolar current pulses per day. The condition of the PEDOT coated electrodes is monitored in between with electrical impedance spectroscopy measurements. The results of this study demonstrate that the PEDOT coated electrodes are stable for more than 3.6 billion bipolar current pulses. Also the unstimulated electrodes show currently no degradation after the time period of 5 months. These results indicate an appropriate long-term stability of this electrode coating for chronic recording and electrical stimulation. The long-term measurements are still continuing to investigate the life limit of this electrode coating.

Keywords: chronic recording, electrical stimulation, long-term stability, microelectrodes, PEDOT

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Authors: Panagiota A. Kotsoni, George S. Ypsilandis

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Learning an L2 is a demanding process for all students and in particular for those with learning disabilities (LD) who demonstrate an inability to catch up with their classmates’ progress in a given period of time. This area of study, i.e. examining children with learning disabilities in L2 has not (yet) attracted the growing interest that is registered in L1 and thus remains comparatively neglected. It is this scientific field that this study wishes to contribute to. The longitudinal purpose of this study is to locate effective Supportive Feedback Strategies (SFS) and add to the quality of learning in second language vocabulary in both typically developing (TD) and LD children. Specifically, this study aims at investigating and comparing the performance of TD with LD children on two different types of SFSs related to vocabulary short and long-term retention. In this study two different SFSs have been examined to a total of ten (10) unknown vocabulary items. Both strategies provided morphosyntactic clarifications upon new contextualized vocabulary items. The traditional SFS (direct) provided the information only in one hypertext page with a selection on the relevant item. The experimental SFS (engaging) provided the exact same split information in three successive hypertext pages in the form of a hybrid dialogue asking from the subjects to move on to the next page by selecting the relevant link. It was hypothesized that this way the subjects would engage in their own learning process by actively asking for more information which would further lead to their better retention. The participants were fifty-two (52) foreign language learners (33 TD and 19 LD) aged from 9 to 12, attending an English language school at the level of A1 (CEFR). The design of the study followed a typical pre-post-post test procedure after an hour and after a week. The results indicated statistically significant group differences with TD children performing significantly better than the LD group in both short and long-term memory measurements and in both SFSs. As regards the effectiveness of one SFS over another the initial hypothesis was not supported by the evidence as the traditional SFS was more effective compared to the experimental one in both TD and LD children. This difference proved to be statistically significant only in the long-term memory measurement and only in the TD group. It may be concluded that the human brain seems to adapt to different SFS although it shows a small preference when information is provided in a direct manner.

Keywords: learning disabilities, memory, second/foreign language acquisition, supportive feedback

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Authors: Yuta Kurashina, Chikahiro Imashiro, Kiyoshi Ohnuma, Kenjiro Takemura

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Research objectives and goals: To realize clinical applications of regenerative medicine, a mass cell culture is highly required. In a conventional cell culture, trypsinization was employed for cell detachment. However, trypsinization causes proliferation decrease due to injury of cell membrane. In order to detach cells using an enzyme-free method, therefore, this study proposes a novel cell detachment method capable of detaching adherent cells using acoustic radiation pressure exposed to the dish by the assistance of serum-free medium with ITS liquid medium supplement. Methods used In order to generate acoustic radiation pressure, a piezoelectric ceramic plate was glued on a glass plate to configure an ultrasonic transducer. The glass plate and a chamber wall compose a chamber in which a culture dish is placed in glycerol. Glycerol transmits acoustic radiation pressure to adhered cells on the culture dish. To excite a resonance vibration of transducer, AC signal with 29-31 kHz (swept) and 150, 300, and 450 V was input to the transducer for 5 min. As a pretreatment to reduce cell adhesivity, serum-free medium with ITS liquid medium supplement was spread to the culture dish before exposed to acoustic radiation pressure. To evaluate the proposed cell detachment method, C2C12 myoblast cells (8.0 × 104 cells) were cultured on a ø35 culture dish for 48 hr, and then the medium was replaced with the serum-free medium with ITS liquid medium supplement for 24 hr. We replaced the medium with phosphate buffered saline and incubated cells for 10 min. After that, cells were exposed to the acoustic radiation pressure for 5 min. We also collected cells by using trypsinization as control. Cells collected by the proposed method and trypsinization were respectively reseeded in ø60 culture dishes and cultured for 24 hr. Then, the number of proliferated cells was counted. Results achieved: By a phase contrast microscope imaging, shrink of lamellipodia was observed before exposed to acoustic radiation pressure, and no cells remained on the culture dish after the exposed of acoustic radiation pressure. This result suggests that serum-free medium with ITS liquid inhibits adhesivity of cells and acoustic radiation pressure detaches cells from the dish. Moreover, the number of proliferated cells 24 hr after collected by the proposed method with 150 and 300 V is the same or more than that by trypsinization, i.e., cells were proliferated 15% higher with the proposed method using acoustic radiation pressure than with the traditional cell collecting method of trypsinization. These results proved that cells were able to be collected by using the appropriate exposure of acoustic radiation pressure. Conclusions: This study proposed a cell detachment method using acoustic radiation pressure by the assistance of serum-free medium. The proposed method provides an enzyme-free cell detachment method so that it may be used in future clinical applications instead of trypsinization.

Keywords: acoustic radiation pressure, cell detachment, enzyme free, ultrasonic transducer

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Authors: John McDowall, Lucy Lightfoot

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Stigma constitutes a significant barrier to the recovery and social integration of individuals affected by mental illness. Although there is some debate in the literature regarding the definition and utility of stigma as a concept, it is widely accepted that it comprises three components: stereotypical beliefs, prejudicial reactions, and discrimination. Stereotypical beliefs describe the cognitive knowledge-based component of stigma, referring to beliefs (often negative) about members of a group that is based on cultural and societal norms (e.g. ‘People with anxiety are just weak’). Prejudice refers to the affective/evaluative component of stigma and describes the endorsement of negative stereotypes and the resulting negative emotional reactions (e.g. ‘People with anxiety are just weak, and they frustrate me’). Discrimination refers to the behavioural component of stigma, which is arguably the most problematic, as it exerts a direct effect on the stigmatized person and may lead people to behave in a hostile or avoidant way towards them (i.e. refusal to hire them). Research exploring anti-stigma initiatives focus primarily on an educational approach, with the view that accurate information will replace misconceptions and decrease stigma. Many approaches take a biogenetic stance, emphasising brain and biochemical deficits - the idea being that ‘mental illness is an illness like any other.' While this approach tends to effectively reduce blame, it has also demonstrated negative effects such as increasing prognostic pessimism, the desire for social distance and perceptions of stereotypes. In the present study 144 participants were split into three groups and read one of three vignettes presenting causal explanations for Generalised Anxiety Disorder (GAD): One explanation emphasized biogenetic factors as being important in the etiology of GAD, another emphasised psychosocial factors (e.g. aversive life events, poverty, etc.), and a third stressed the adaptive features of the disorder from an evolutionary viewpoint. A variety of measures tapping the various components of stigma were administered following the vignettes. No difference in stigma measures as a function of causal explanation was found. People who had contact with mental illness in the past were significantly less stigmatising across a wide range of measures, but this did not interact with the type of causal explanation.

Keywords: generalised anxiety disorder, discrimination, prejudice, stigma

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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Authors: Hebah M. Musalem, Jeylan El-Mansoury, Lin M. Tuleimat, Selwa Alhazza, Abdul-Aziz A. Al Zoba

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Background: Amblyopia is a condition that affects the visual system triggering a decrease in visual acuity without a known underlying pathology. It is due to abnormal vision development in childhood or infancy. Most importantly, vision loss is preventable or reversible with the right kind of intervention in most of the cases. Strabismus, sensory defects, and anisometropia are all well-known causes of amblyopia. However, ocular misalignment in Strabismus is considered the most common form of amblyopia worldwide. The risk of developing amblyopia increases in premature children, developmentally delayed or children who had brain lesions affecting the visual pathway. The prevalence of amblyopia varies between 2 to 5 % in the world according to the literature. Objective: To determine the different causes of Amblyopia in pediatric patients seen in ophthalmology clinic of a tertiary care center, i.e. King Faisal Specialist Hospital and Research Center (KFSH&RC). Methods: This is a hospital based, random retrospective, based on reviewing patient’s files in the Ophthalmology Department of KFSH&RC in Riyadh city, Kingdom of Saudi Arabia. Inclusion criteria: amblyopic pediatric patients who attended the clinic from 2015 to 2016, who are between 6 months and 18 years old. Exclusion Criteria: patients above 18 years of age and any patient who is uncooperative to obtain an accurate vision or a proper refraction. Detailed ocular and medical history are recorded. The examination protocol includes a full ocular exam, full cycloplegic refraction, visual acuity measurement, ocular motility and strabismus evaluation. All data were organized in tables and graphs and analyzed by statistician. Results: Our preliminary results will be discussed on spot by our corresponding author. Conclusions: We focused on this study on utilizing various examination techniques which enhanced our results and highlighted a distinguished correlation between amblyopia and its’ causes. This paper recommendation emphasizes on critical testing protocols to be followed among amblyopic patient, especially in tertiary care centers.

Keywords: amblyopia, amblyopia causes, amblyopia diagnostic criterion, amblyopia prevalence, Saudi Arabia

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Authors: Taku Numao, Kazu Amimoto, Tomoko Shimada, Kyohei Ichikawa

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Background: Unilateral spatial neglect (USN) is a common syndrome following damage to one hemisphere of the brain (usually the right side), in which a patient fails to report or respond to stimulation from the contralesional side. These symptoms are not due to primary sensory or motor deficits, but instead, reflect an inability to process input from that side of their environment. Prism adaptation (PA) is a therapeutic treatment for USN, wherein a patient’s visual field is artificially shifted laterally, resulting in a sensory-motor adaptation. However, patients with USN also tend to perceive a left-leaning subjective vertical in the frontal plane. The traditional PA cannot be used to correct a tilt in the subjective vertical, because a prism can only polarize, not twist, the surroundings. However, this can be accomplished using a head mounted display (HMD) and a web-camera. Therefore, this study investigated whether an HMD system could be used to correct the spatial perception of USN patients in the frontal as well as the horizontal plane. We recruited healthy subjects in order to collect data for the refinement of USN patient therapy. Methods: Eight healthy subjects sat on a chair wearing a HMD (Oculus rift DK2), with a web-camera (Ovrvision) displaying a 10 degree leftward rotation and a 10 degree counter-clockwise rotation along the frontal plane. Subjects attempted to point a finger at one of four targets, assigned randomly, a total of 48 times. Before and after the intervention, each subject’s body-centre judgment (BCJ) was tested by asking them to point a finger at a touch panel straight in front of their xiphisternum, 10 times sight unseen. Results: Intervention caused the location pointed to during the BCJ to shift 35 ± 17 mm (Ave ± SD) leftward in the horizontal plane, and 46 ± 29 mm downward in the frontal plane. The results in both planes were significant by paired-t-test (p<.01). Conclusions: The results in the horizontal plane are consistent with those observed following PA. Furthermore, the HMD and web-camera were able to elicit 3D effects, including in both the horizontal and frontal planes. Future work will focus on applying this method to patients with and without USN, and investigating whether subject posture is also affected by the HMD system.

Keywords: head mounted display, posture, prism adaptation, unilateral spatial neglect

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Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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Authors: Martonovich Noa, Maman David, Alfandari Liad, Behrbalk Eyal.

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Introduction: The human body is designed for upright standing and walking, with the lower extremities and axial skeleton supporting weight-bearing. Constant weight-bearing on joints not meant for this action can lead to various pathologies, as seen in wheelchair users. Handstand practitioners use their wrists as weight-bearing joints during activities, but little is known about wrist injuries in this population. This study aims to investigate the epidemiology of wrist pain among handstand practitioners, as no such data currently exist. Methods: The study is a cross-sectional online survey conducted among athletes who regularly practice handstands. Participants were asked to complete a three-part questionnaire regarding their workout regimen, training habits, and history of wrist pain. The inclusion criteria were athletes over 18 years old who practice handstands more than twice a month for at least 4 months. All data were collected using Google Forms, organized and anonymized using Microsoft Excel, and analyzed using IBM SPSS 26.0. Descriptive statistics were calculated, and potential risk factors were tested using asymptotic t-tests and Fisher's tests. Differences were considered significant when p < 0.05. Results: This study surveyed 402 athletes who regularly practice handstands to investigate the prevalence of chronic wrist pain and potential risk factors. The participants had a mean age of 31.3 years, with most being male and having an average of 5 years of training experience. 56% of participants reported chronic wrist pain, and 14.4% reported a history of distal radial fracture. Yoga was the most practiced form, followed by Capoeira. No significant differences were found in demographic data between participants with and without chronic wrist pain, and no significant associations were found between chronic wrist pain prevalence and warm-up routines or protective aids. Conclusion: The lower half of the body is meant to handle weight-bearing and impact, while transferring the load to upper extremities can lead to various pathologies. Athletes who perform handstands are particularly prone to chronic wrist pain, which affects over half of them. Warm-up sessions and protective instruments like wrist braces do not seem to prevent chronic wrist pain, and there are no significant differences in age or training volume between athletes with and without the condition. Further research is needed to understand the causes of chronic wrist pain in athletes, given the growing popularity of sports and activities that can cause this type of injury.

Keywords: handstand, handbalance, wrist pain, hand and wrist surgery, yoga, calisthenics, circus, capoeira, movement.

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Authors: E. Gopi, E. Devaindran

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Objective: Non-operative management of blunt splenic trauma have started to overtake the traditional splenectomy in recent years across the grade of splenic injury. The two main non-operative methods are observation and angioembolisation. However, the post management convalescence in these groups are still being investigated. The study attempts to quantify the clinical indicators among the two in particular complications, mortalities, conversions to operative management and duration of inpatient stay. Methodology: A systematic search was done via PUBMED, MEDLINE, and EMBASE. A total of 639 articles identified and subsequently 68 articles were identified post duplicates, full text, and inclusion and exclusion criteria. Main exclusions were non-English articles without English translation, pure observational or angioembolisation articles of which no comparison data could be identified and articles looking into pure hemodynamically unstable patients. Results: 24 non randomized controlled trial, 5 clinical control trial and 39 retrospective studies analyzing a total of 23700 patients with blunt splenic trauma. Discrepancies in data were noted in the group who had observational management versus angioembolisation in particular as data was compared among the classes of splenic rupture, the protocol of management in different centers, availability of angiogram suite, and the study design. Further variability was also noted in the angioembolisation arm as the preference for treatment differs between distal versus proximal splenic artery involvement. Overall the cumulative mortality in both observational and angioembolisation group were similar, 2.78% and 5.97% respectively. The cause of death however is not directly attributed to the management itself but rather patient comorbidities, other associated injuries and conversions to splenectomy leading to post splenectomy complications. The cumulative morbidity among each group appears to be same approximately 12% in observational versus 15% in angioembolisation. However, the type of complications varies with the observational group having higher rates of inpatient stay and intrabdominal hematoma infection and angioembolisation group developing more splenic infarcts and bleeds. There were significant disparity in reporting the actual data on duration of inpatient stay and complications to allow a statistically significant quantitative analysis to be done, 15 articles however are currently being considered. Conclusions: Observational management appears to be much effective in managing lower grade splenic trauma (grade 1 and 2) where else angioembolisation appears to play a bigger role in intermediate grades (grade 3-4) in ensuring splenic function preservation. Care has to be taken however in the angioembolisation group in view of distal splenic infarct group compromising splenic function. The cumulated data of 15 articles are now being considered for a meta-analysis.

Keywords: blunt splenic trauma, conservative, non-operative, angioembolisation

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Authors: Anoop T. R., Otman Basir, Robert F. Hess, Eileen E. Birch, Brooke A. Koritala, Reed M. Jost, Becky Luu, David Stager, Ben Thompson

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Strabismus refers to a misalignment of the eyes. Early detection and treatment of strabismus in childhood can prevent the development of permanent vision loss due to abnormal development of visual brain areas. We developed a two-stage method for strabismus detection and classification based on photographs of the face. The first stage detects the presence or absence of strabismus, and the second stage classifies the type of strabismus. The first stage comprises face detection using Haar cascade, facial landmark estimation, face alignment, aligned face landmark detection, segmentation of the eye region, and detection of strabismus using VGG 16 convolution neural networks. Face alignment transforms the face to a canonical pose to ensure consistency in subsequent analysis. Using facial landmarks, the eye region is segmented from the aligned face and fed into a VGG 16 CNN model, which has been trained to classify strabismus. The CNN determines whether strabismus is present and classifies the type of strabismus (exotropia, esotropia, and vertical deviation). If stage 1 detects strabismus, the eye region image is fed into stage 2, which starts with the estimation of pupil center coordinates using mask R-CNN deep neural networks. Then, the distance between the pupil coordinates and eye landmarks is calculated along with the angle that the pupil coordinates make with the horizontal and vertical axis. The distance and angle information is used to characterize the degree and direction of the strabismic eye misalignment. This model was tested on 100 clinically labeled images of children with (n = 50) and without (n = 50) strabismus. The True Positive Rate (TPR) and False Positive Rate (FPR) of the first stage were 94% and 6% respectively. The classification stage has produced a TPR of 94.73%, 94.44%, and 100% for esotropia, exotropia, and vertical deviations, respectively. This method also had an FPR of 5.26%, 5.55%, and 0% for esotropia, exotropia, and vertical deviation, respectively. The addition of one more feature related to the location of corneal light reflections may reduce the FPR, which was primarily due to children with pseudo-strabismus (the appearance of strabismus due to a wide nasal bridge or skin folds on the nasal side of the eyes).

Keywords: strabismus, deep neural networks, face detection, facial landmarks, face alignment, segmentation, VGG 16, mask R-CNN, pupil coordinates, angle deviation, horizontal and vertical deviation

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Authors: Christine Lassen, Elizabeth Leonard, Matthew Oliver

Abstract:

The management of trauma is often complex and outcomes dependent on clinical expertise, effective teamwork, and a supported trauma system. The implementation of a statewide trauma education program should be accessible to all clinicians who manage trauma, but this can be challenging due to diverse individual needs, trauma service needs and geography. The NSW Institute of Trauma and Injury Management (ITIM) is a government funded body, responsible for coordinating and supporting the NSW Trauma System. The aim of this presentation is to describe how education initiatives have been implemented across the state. Simulation: In 2006, ITIM developed a Trauma Team Training Course - aimed to educate clinicians on the technical and non-technical skills required to manage trauma. The course is now independently coordinated by trauma services across the state at major trauma centres as well as in regional and rural hospitals. ITIM is currently in the process of re-evaluating and updating the Trauma Team Training Course to allow for the development of new resources and simulation scenarios. Trauma Education Evenings: In 2013, ITIM supported major trauma services to develop trauma education evenings which allowed the provision of free education to staff within the area health service and local area. The success of these local events expanded to regional hospitals. A total of 75 trauma education evenings have been conducted within NSW, with over 10,000 attendees. Wed-Based Resources: Recently, ITIM commenced free live streaming of the trauma education evenings which have now had over 3000 live views. The Trauma App developed in 2015 provides trauma clinicians with a centralised portal for trauma information and works on smartphones and tablets that integrate with the ITIM website. This supports pre-hospital and bedside clinical decisions and allows for trauma care to be more standardised, evidence-based, timely, and appropriate. Online e-Learning modules have been developed to assist clinicians, reduce unwarranted clinical variation and provide up to date evidence based education. The modules incorporate clinically focused education content with summative and formative assessments. Conclusion: Since 2005, ITIM has helped to facilitate the development of trauma education programs for doctors, nurses, pre-hospital and allied health clinicians. ITIM has been actively involved in more than 100 specialized trauma education programs, seminars and clinical workshops - attended by over 12,000 staff. The provision of state-wide trauma education is a challenging task requiring collaboration amongst numerous agencies working towards a common goal – to provide easily accessible trauma education.

Keywords: education, simulation, team-training, trauma

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Authors: Bahar Hazal Yalçınkaya, Bayram Yılmaz, Mustafa Özilgen

Abstract:

Brain information transmission in the neuronal network occurs in the form of electrical signals. Neural work transmits information between the neurons or neurons and target cells by moving charged particles in a voltage field; a fraction of the energy utilized in this process is dissipated via entropy generation. Exergy loss and entropy generation models demonstrate the inefficiencies of the communication along the dendritic trees. In this study, neurons of 4 different animals were analyzed with one dimensional cable model with N=6 identical dendritic trees and M=3 order of symmetrical branching. Each branch symmetrically bifurcates in accordance with the 3/2 power law in an infinitely long cylinder with the usual core conductor assumptions, where membrane potential is conserved in the core conductor at all branching points. In the model, exergy loss and entropy generation rates are calculated for each branch of equivalent cylinders of electrotonic length (L) ranging from 0.1 to 1.5 for four different dendritic branches, input branch (BI), and sister branch (BS) and two cousin branches (BC-1 & BC-2). Thermodynamic analysis with the data coming from two different cat motoneuron studies show that in both experiments nearly the same amount of exergy is lost while generating nearly the same amount of entropy. Guinea pig vagal motoneuron loses twofold more exergy compared to the cat models and the squid exergy loss and entropy generation were nearly tenfold compared to the guinea pig vagal motoneuron model. Thermodynamic analysis show that the dissipated energy in the dendritic tress is directly proportional with the electrotonic length, exergy loss and entropy generation. Entropy generation and exergy loss show variability not only between the vertebrate and invertebrates but also within the same class. Concurrently, single action potential Na⁺ ion load, metabolic energy utilization and its thermodynamic aspect contributed for squid giant axon and mammalian motoneuron model. Energy demand is supplied to the neurons in the form of Adenosine triphosphate (ATP). Exergy destruction and entropy generation upon ATP hydrolysis are calculated. ATP utilization, exergy destruction and entropy generation showed differences in each model depending on the variations in the ion transport along the channels.

Keywords: ATP utilization, entropy generation, exergy loss, neuronal information transmittance

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Authors: Dalia El Hadi, Alaa Bou Ghannam, Hala Mostafa, Hana Mansour, Ibrahim Hashim, Soubhi Tahhan, Tharwat El Zahran

Abstract:

Introduction: Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. Some would require neuroimaging. Most commonly used are the CT and MRI of the Brain. They can be over-used when not indicated. Their yield remains dependent on multiple factors relating to the clinical scenario. Methods: A retrospective cross-sectional study was conducted by reviewing the electronic medical records of patients presenting to the Emergency Department (ED) with isolated neuro-ophthalmologic complaints. For each patient, data were collected on the clinical presentation, whether neuroimaging was performed (and which type), and the result of neuroimaging. Analysis of the performed neuroimaging was made, and its yield was determined. Results: A total of 211 patients were reviewed. The complaints or symptoms at presentation were: blurry vision, change in the visual field, transient vision loss, floaters, double vision, eye pain, eyelid droop, headache, dizziness and others such as nausea or vomiting. In the ED, a total of 126 neuroimaging procedures were performed. Ninety-four imagings (74.6%) were normal, while 32 (25.4%) had relevant abnormal findings. Only 2 symptoms were significant for abnormal imaging: blurry vision (p-value= 0.038) and visual field change (p-value= 0.014). While 4 physical exam findings had significant abnormal imaging: visual field defect (p-value= 0.016), abnormal pupil reactivity (p-value= 0.028), afferent pupillary defect (p-value= 0.018), and abnormal optic disc exam (p-value= 0.009). Conclusion: Risk indicators for abnormal neuroimaging in the setting of neuro-ophthalmological emergencies are blurred vision or changes in the visual field on history taking. While visual field irregularities, abnormal pupil reactivity with or without afferent pupillary defect, or abnormal optic discs, are risk factors related to physical testing. These findings, when present, should sway the ED physician towards neuroimaging but still individualizing each case is of utmost importance to prevent time-consuming, resource-draining, and sometimes unnecessary workup. In the end, it suggests a well-structured patient-centered algorithm to be followed by ED physicians.

Keywords: emergency department, neuro-ophthalmology, neuroimaging, risk indicators

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Authors: Scott Andersen

Abstract:

Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

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Authors: Lubna M. Al-Otaibi

Abstract:

Mucocele is a common benign neoplasm of the oral cavity and the most common after fibroma. The lesion develops as a result of retention or extravasation of mucous material from minor salivary glands. Extravasation type of mucocele results from trauma and mostly occurs in the lower lip of young patients. The various treatment options available for the treatment of mucocele are associated with a relatively high incidence of recurrence making surgical intervention necessary for a permanent cure. The conventional surgical procedure, however, arouses apprehension in the patient and is associated with bleeding and postoperative pain. Recently, treatment of mucocele with lasers has become a viable treatment option. Various types of lasers are being used and are preferable over the conventional surgical procedure as they provide good hemostasis, reduced postoperative swelling and pain, reduced bacterial population, lesser need for suturing, faster healing and low recurrence rates. Er,Cr:YSGG is a solid-state laser with great affinity to water molecule. Its hydrokinetic cutting action allows it to work effectively on hydrated tissues without any thermal damage. However, up to date, only a few studies have reported its use in the removal of lip mucocele, especially in children. In this case, a 6 year old female patient with history of trauma to the lower lip presented with a soft, sessile, whitish-bluish 4 mm papule. The lesion was present for approximately four months and was fluctuant in size. The child developed a habit of biting the lesion causing injury, bleeding and discomfort. Surgical excision under local anaesthesia was performed using 2780 nm Er,Cr:YSGG Laser (WaterLase iPlus, Irvine, CA) with a Gold handpiece and MZ6 tip (3.5w, 50 Hz, 20% H2O, 20% Air, S mode). The tip was first applied in contact mode with focused beam using the Circumferential Incision Technique (CIT) to excise the tissue followed by the removal of the underlying causative minor salivary gland. Bleeding was stopped using Laser Dry Bandage setting (0.5w, 50 Hz, 1% H2O, 20% Air, S mode) and no suturing was needed. Safety goggles were worn and high-speed suction was used for smoke evacuation. Mucocele excision using 2780 nm Er,Cr:YSGG laser was rapid, easy to perform with excellent precision and allowed for histopathological examination of the excised tissue. The patient was comfortable and there were minimum bleeding and no sutures, postoperative pain, scarring or recurrence. Laser assisted mucocele excision appears to have efficient and reliable benefits in young patients and should be considered as an alternative to conventional surgical and non-surgical techniques.

Keywords: Erbium, excision, laser, lip, mucocele

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

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Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

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Authors: Tracey Lion-Cachet

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Eating disorders typically manifest in adolescence and are notoriously difficult to treat. There are two notable reasons for this. Firstly, research consistently demonstrates that early intervention is a critical mediator of prognosis, with early intervention leading to a better prognosis. However, because eating disorders do not originate as full-syndrome diagnoses but rather as prodromal cases, they often go undetected; by the time symptoms meet diagnostic criteria, they have become recalcitrant. Another interrelated issue is motivation to change. Research demonstrates that in the early stages of an eating disorder, adolescents are highly resistant to change, and motivation increases only once symptoms have shifted from egosyntonic to egodystonic in nature. The purpose of this project was to design a prevention model based on the social psychology paradigm of Entertainment-Education, which embeds messages within the genre of film as a means of affecting change. The resulting project was a narrative screenplay targeting teenagers/young adults from diverse backgrounds. The goals of the project were to create a film script that, if ultimately made into a film, could serve to: 1) interrupt symptom progression and improve prognosis through early intervention; 2) incorporate techniques from third-wave cognitive behavioral treatment models, acceptance and commitment therapy (ACT) and rational recovery (RR), with a focus on the effects of mindfulness as a means of informing recovery; 3) target issues to do with motivation to change by shifting the perception of eating disorders from culturally specific psychiatric illnesses to habit-based brain wiring issues. Nine licensed clinicians were asked to evaluate two excerpts taken from the final script. They subsequently provided feedback on a Likert-scale, which assessed whether the script had achieved its goals. Overall, evaluators agreed that the project’s etiological and intervention models have the potential to inspire change and serve as an effective means of prevention and treatment of eating disorders. However, one-third of the evaluators did not find the content developmentally appropriate. This is a notable limitation to the study and will need to be addressed in the larger script before the final project can potentially be targeted to a teenage and young adult audience.

Keywords: adolescents, eating disorders, pediatrics, entertainment-education, mindfulness-based intervention, prevention

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Authors: Weeradej Cheewapattananuwong, Keeree Srivichian, Godchamon Somchai, Wasin Phusanong, Nontawat Yoddamnern

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Natural rubber used for traffic devices in Thailand has been developed and researched for several years. When compared with Dry Rubber Content (DRC), the quality of Rib Smoked Sheet (RSS) is better. However, the cost of admixtures, especially CaCO₃ and sulphur, is higher than the cost of RSS itself. In this research, Flexible Guideposts and Rubber Fender Barriers (RFB) are taken into consideration. In case of flexible guideposts, the materials used are both RSS and DRC60%, but for RFB, only RSS is used due to the controlled performance tests. The objective of flexible guideposts and RFB is to decrease a number of accidents, fatal rates, and serious injuries. Functions of both devices are to save road users and vehicles as well as to absorb impact forces from vehicles so as to decrease of serious road accidents. This leads to the mitigation methods to remedy the injury of motorists, form severity to moderate one. The solution is to find the best practice of traffic devices using natural rubber under the engineering concepts. In addition, the performances of materials, such as tensile strength and durability, are calculated for the modulus of elasticity and properties. In the laboratory, the simulation of crashes, finite element of materials, LRFD, and concrete technology methods are taken into account. After calculation, the trials' compositions of materials are mixed and tested in the laboratory. The tensile test, compressive test, and weathering or durability test are followed and based on ASTM. Furthermore, the Cycle-Repetition Test of Flexible Guideposts will be taken into consideration. The final decision is to fabricate all materials and have a real test section in the field. In RFB test, there will be 13 crash tests, 7 Pickup Truck tests, and 6 Motorcycle Tests. The test of vehicular crashes happens for the first time in Thailand, applying the trial and error methods; for example, the road crash test under the standard of NCHRP-TL3 (100 kph) is changed to the MASH 2016. This is owing to the fact that MASH 2016 is better than NCHRP in terms of speed, types, and weight of vehicles and the angle of crash. In the processes of MASH, Test Level 6 (TL-6), which is composed of 2,270 kg Pickup Truck, 100 kph, and 25 degree of crash-angle is selected. The final test for real crash will be done, and the whole system will be evaluated again in Korea. The researchers hope that the number of road accidents will decrease, and Thailand will be no more in the top tenth ranking of road accidents in the world.

Keywords: LRFD, load and resistance factor design, ASTM, american society for testing and materials, NCHRP, national cooperation highway research program, MASH, manual for assessing safety hardware

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Authors: Karan Sharma, Ajay Kumar

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Epileptic seizure is a type of disease due to which electrical charge in the brain flows abruptly resulting in abnormal activity by the subject. One percent of total world population gets epileptic seizure attacks.Due to abrupt flow of charge, EEG (Electroencephalogram) waveforms change. On the display appear a lot of spikes and sharp waves in the EEG signals. Detection of epileptic seizure by using conventional methods is time-consuming. Many methods have been evolved that detect it automatically. The initial part of this paper provides the review of techniques used to detect epileptic seizure automatically. The automatic detection is based on the feature extraction and classification patterns. For better accuracy decomposition of the signal is required before feature extraction. A number of parameters are calculated by the researchers using different techniques e.g. approximate entropy, sample entropy, Fuzzy approximate entropy, intrinsic mode function, cross-correlation etc. to discriminate between a normal signal & an epileptic seizure signal.The main objective of this review paper is to present the variations in the EEG signals at both stages (i) Interictal (recording between the epileptic seizure attacks). (ii) Ictal (recording during the epileptic seizure), using most appropriate methods of analysis to provide better healthcare diagnosis. This research paper then investigates the effects of a noninvasive healing therapy on the subjects by studying the EEG signals using latest signal processing techniques. The study has been conducted with Reiki as a healing technique, beneficial for restoring balance in cases of body mind alterations associated with an epileptic seizure. Reiki is practiced around the world and is recommended for different health services as a treatment approach. Reiki is an energy medicine, specifically a biofield therapy developed in Japan in the early 20th century. It is a system involving the laying on of hands, to stimulate the body’s natural energetic system. Earlier studies have shown an apparent connection between Reiki and the autonomous nervous system. The Reiki sessions are applied by an experienced therapist. EEG signals are measured at baseline, during session and post intervention to bring about effective epileptic seizure control or its elimination altogether.

Keywords: EEG signal, Reiki, time consuming, epileptic seizure

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Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

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Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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