Search results for: Brain scan

Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Deborah Zelinsky

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The retina filters millions of incoming signals into a smaller amount of exiting optic nerve fibers that travel to different portions of the brain. Most of the signals are for eyesight (called "image-forming" signals). However, there are other faster signals that travel "elsewhere" and are not directly involved with eyesight (called "non-image-forming" signals). This article centers on the neurons of the optic nerve connecting to parts of the limbic system. Eye care providers are currently looking at parvocellular and magnocellular processing pathways without realizing that those are part of an enormous "galaxy" of all the body systems. Lenses are modifying both non-image and image-forming pathways, taking A.M. Skeffington's seminal work one step further. Almost 100 years ago, he described the Where am I (orientation), Where is It (localization), and What is It (identification) pathways. Now, among others, there is a How am I (animation) and a Who am I (inclination, motivation, imagination) pathway. Classic eye testing considers pupils and often assesses posture and motion awareness, but classical prescriptions often overlook limbic involvement in visual processing. The limbic system is composed of the hippocampus, amygdala, hypothalamus, and anterior nuclei of the thalamus. The optic nerve's limbic connections arise from the intrinsically photosensitive retinal ganglion cells (ipRGC) through the "retinohypothalamic tract" (RHT). There are two main hypothalamic nuclei with direct photic inputs. These are the suprachiasmatic nucleus and the paraventricular nucleus. Other hypothalamic nuclei connected with retinal function, including mood regulation, appetite, and glucose regulation, are the supraoptic nucleus and the arcuate nucleus. The retino-hypothalamic tract is often overlooked when we prescribe eyeglasses. Each person is different, but the lenses we choose are influencing this fast processing, which affects each patient's aiming and focusing abilities. These signals arise from the ipRGC cells that were only discovered 20+ years ago and do not address the campana retinal interneurons that were only discovered 2 years ago. As eyecare providers, we are unknowingly altering such factors as lymph flow, glucose metabolism, appetite, and sleep cycles in our patients. It is important to know what we are prescribing as the visual processing evaluations expand past the 20/20 central eyesight.

Keywords: neuromodulation, retinal processing, retinohypothalamic tract, limbic system, visual processing

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Authors: Geetha Jayapathy, Lakshmi Muthukrishnan, Manoj Kumar Reddy Pulim , Radhika Raman

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Introduction: Ketones are the end products of fatty acid metabolism and a source of energy for vital organs such as the brain, heart and skeletal muscles. Ketones are produced in excess when glucose is not available as a source of energy or it cannot be utilized as in diabetic ketoacidosis. Children admitted in the emergency department often have starvation ketosis which is not clinically manifested. Decision on admission of children to the emergency room with subtle signs can be difficult at times. Point of care blood ketone testing can be done at the bedside even in a primary level care setting to supplement and guide us in our management decisions. Hence this study was done to explore the utility of this simple bedside parameter as a supplement in assessing pediatric patients presenting to the emergency department. Objectives: To estimate blood ketones of children admitted in the emergency department. To analyze the significance of blood ketones in various disease conditions. Methods: Blood ketones using point of care testing instrument (ABOTTprecision Xceed Pro meters) was done in patients getting admitted in emergency room and in out-patients (through sample collection centre). Study population: Children aged 1 month to 18 years were included in the study. 250 cases (In-patients) and 250 controls (out-patients) were collected. Study design: Prospective observational study. Data on details of illness and physiological status were documented. Blood ketones were compared between the two groups and all in patients were categorized into various system groups and analysed. Results: Mean blood ketones were high in in-patients ranging from 0 to 7.2, with a mean of 1.28 compared to out-patients ranging from 0 to 1.9 with a mean of 0.35. This difference was statistically significant with a p value < 0.001. In-patients with shock (mean of 4.15) and diarrheal dehydration (mean of 1.85) had a significantly higher blood ketone values compared to patients with other system involvement. Conclusion: Blood ketones were significantly high (above the normal range) in pediatric patients who are sick requiring admission. Patients with various forms of shock had very high blood ketone values as found in diabetic ketoacidosis. Ketone values in diarrheal dehydration were moderately high correlating to the degree of dehydration.

Keywords: admission, blood ketones, paediatric emergencies, point of care testing

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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: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

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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: Ahmedou Moulaye Idriss, Yahya Tfeil

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Medical imaging technology has become an indispensable tool in many branches of the biomedical, health area, and research and is vitally important for the training of professionals in these fields. It is not only about the tools, technologies, and knowledge provided but also about the community that this training project proposes. In order to be able to raise the level of anatomy teaching in the medical school of Nouakchott in Mauritania, it is necessary and even urgent to facilitate access to modern technology for African countries. The role of technology as a key driver of justifiable development has long been recognized. Anatomy is an essential discipline for the training of medical students; it is a key element for the training of medical specialists. The quality and results of the work of a young surgeon depend on his better knowledge of anatomical structures. The teaching of anatomy is difficult as the discipline is being neglected by medical students in many academic institutions. However, anatomy remains a vital part of any medical education program. When anatomy is presented in various planes medical students approve of difficulties in understanding. They do not increase their ability to visualize and mentally manipulate 3D structures. They are sometimes not able to correctly identify neighbouring or associated structures. This is the case when they have to make the identification of structures related to the caudate lobe when the liver is moved to different positions. In recent decades, some modern educational tools using digital sources tend to replace old methods. One of the main reasons for this change is the lack of cadavers in laboratories with poorly qualified staff. The emergence of increasingly sophisticated mathematical models, image processing, and visualization tools in biomedical imaging research have enabled sophisticated three-dimensional (3D) representations of anatomical structures. In this paper, we report our current experience in the Faculty of Medicine in Nouakchott Mauritania. One of our main aims is to create a local learning community in the fields of anatomy. The main technological platform used in this project is called 3D Slicer. 3D Slicer platform is an open-source application available for free for viewing, analysis, and interaction with biomedical imaging data. Using the 3D Slicer platform, we created from real medical images anatomical atlases of parts of the human body, including head, thorax, abdomen, liver, and pelvis, upper and lower limbs. Data were collected from several local hospitals and also from the website. We used MRI and CT-Scan imaging data from children and adults. Many different anatomy atlases exist, both in print and digital forms. Anatomy Atlas displays three-dimensional anatomical models, image cross-sections of labelled structures and source radiological imaging, and a text-based hierarchy of structures. Open and free online anatomical atlases developed by our anatomy laboratory team will be available to our students. This will allow pedagogical autonomy and remedy the shortcomings by responding more fully to the objectives of sustainable local development of quality education and good health at the national level. To make this work a reality, our team produced several atlases available in our faculty in the form of research projects.

Keywords: anatomy, education, medical imaging, three dimensional

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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: Noman Shahzad, Amyn Pardhan, Hasnain Zafar

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Introduction: Though short term survival advantage of damage control laparotomy in management of critically ill trauma patients is established, there is little known about the long-term quality of life of these patients. Facial closure rate after damage control laparotomy is reported to be 20-70 percent. Abdominal wall reconstruction in those who failed to achieve facial closure is challenging and can potentially affect quality of life of these patients. Methodology: We conducted retrospective matched cohort study. Adult patients who underwent damage control laparotomy from Jan 2007 till Jun 2013 were identified through medical record. Patients who had concomitant disabling brain injury or limb injuries requiring amputation were excluded. Age, gender and presentation time matched non exposure group of patients who underwent laparotomy for trauma but no damage control were identified for each damage control laparotomy patient. Quality of life assessment was done via telephonic interview at least one year after the operation, using Urdu version of EuroQol Group Quality of Life (QOL) questionnaire EQ5D after permission. Wilcoxon signed rank test was used to compare QOL scores and McNemar test was used to compare individual parameters of QOL questionnaire. Study was approved by institutional ethical review committee. Results: Out of 32 patients who underwent damage control laparotomy during study period, 20 fulfilled the selection criteria for which 20 matched controls were selected. Median age of patients (IQ Range) was 33 (26-40) years. Facial closure rate in damage control laparotomy group was 40% (8/20). One third of those who did not achieve facial closure (4/12) underwent abdominal wall reconstruction. Self-reported QOL score of damage control laparotomy patients was significantly worse than non-damage control group (p = 0.032). There was no statistically significant difference in two groups regarding individual QOL measures. Significantly, more patients in damage control group were requiring use of abdominal binder, and more patients in damage control group had to either change their job or had limitations in continuing previous job. Our study was not adequately powered to detect factors responsible for worse QOL in damage control group. Conclusion: Quality of life of damage control patients is worse than their age and gender matched patients who underwent trauma laparotomy but not damage control. Adequately powered studies need to be conducted to explore factors responsible for this finding for potential improvement.

Keywords: damage control laparotomy, laparostomy, quality of life

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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: 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: David Philpott, Karen Kennedy

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In recognition of an increasingly diverse student population, a Teaching and Learning Framework was developed at Memorial University of Newfoundland. This framework emphasizes work that is engaging, supportive, inclusive, responsive, committed to discovery, and is outcomes-oriented for both educators and learners. The goal of the Teaching and Learning framework was to develop a number of initiatives that builds on existing knowledge, proven programs, and existing supports in order to respond to the specific needs of identified groups of diverse learners: 1) academically vulnerable first year students; 2) students with individual learning needs associated with disorders and/or mental health issues; 3) international students and those from non-western cultures. This session provides an overview of this process. The strategies employed to develop these initiatives were drawn primarily from research on student success and retention (literature review), information on pre-existing programs (environmental scan), an analysis of in-house data on students at our institution; consultations with key informants at all of Memorial’s campuses. The first initiative that emerged from this research was a pilot project proposal for a first-year success program in support of the first-year experience of academically vulnerable students. This program offers a university experience that is enhanced by smaller classes, supplemental instruction, learning communities, and advising sessions. The second initiative that arose under the mandate of the Teaching and Learning Framework was a collaborative effort between two institutions (Memorial University and the College of the North Atlantic). Both institutions participated in a shared conversation to examine programs and services that support an accessible and inclusive environment for students with disorders and/or mental health issues. A report was prepared based on these conversations and an extensive review of research and programs across the country. Efforts are now being made to explore possible initiatives that address culturally diverse and non-traditional learners. While an expanding literature has emerged on diversity in higher education, the process of developing institutional initiatives is usually excluded from such discussions, while the focus remains on effective practice. The proposals that were developed constitute a co-ordination and strengthening of existing services and programs; a weaving of supports to engage a diverse body of students in a sense of community. This presentation will act as a guide through the process of developing projects addressing learner diversity and engage attendees in a discussion of institutional practices that have been implemented in support of overcoming challenges, as well as provide feedback on institutional and student outcomes. The focus of this session will be on effective practice, and will be of particular interest to university administrators, educational developers, and educators wishing to implement similar initiatives on their campuses; possible adaptations for practice will be addressed. A presentation of findings from this research will be followed by an open discussion where the sharing of research, initiatives, and best practices for the enhancement of teaching and learning is welcomed. There is much insight and understanding to be gained through the sharing of ideas and collaborative practice as we move forward to further develop the program and prepare other initiatives in support of diversity and inclusion.

Keywords: eco-scale, green analysis, environmentally-friendly, pharmaceuticals analysis

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Authors: Paul Licina, Emma M. Johnston, David Lisle, Mark Young, Chris Brady

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Background: Lumbar pars pathology is a common cause of pain in the growing spine. It can be seen in young athletes participating in at-risk sports and can affect sporting performance and long-term health due to its resistance to traditional management. There is a current lack of consensus of classification and treatment for pars injuries. Previous systems used CT to stage pars defects but could not assess early stress reactions. A modified classification is proposed that considers findings on MRI, significantly improving early treatment guidance. The treatment protocol is designed for patients aged 5 to 19 years. Method: Clinical screening identifies patients with a low, medium, or high index of suspicion for lumbar pars injury using patient age, sport participation and pain characteristics. MRI of the at-risk cohort enables augmentation of existing CT-based classification while avoiding ionising radiation. Patients are classified into five categories based on MRI findings. A type 0 lesion (stress reaction) is present when CT is normal and MRI shows high signal change (HSC) in the pars/pedicle on T2 images. A type 1 lesion represents the ‘early defect’ CT classification. The group previously referred to as a 'progressive stage' defect on CT can be split into 2A and 2B categories. 2As have HSC on MRI, whereas 2Bs do not. This distinction is important with regard to healing potential. Type 3 lesions are terminal stage defects on CT, characterised by pseudarthrosis. MRI shows no HSC. Results: Stress reactions (type 0) and acute fractures (1 and 2a) can heal and are treated in a custom-made hard brace for 12 weeks. It is initially worn 23 hours per day. At three weeks, patients commence basic core rehabilitation. At six weeks, in the absence of pain, the brace is removed for sleeping. Exercises are progressed to positions of daily living. Patients with continued pain remain braced 23 hours per day without exercise progression until becoming symptom-free. At nine weeks, patients commence supervised exercises out of the brace for 30 minutes each day. This allows them to re-learn muscular control without rigid support of the brace. At 12 weeks, bracing ceases and MRI is repeated. For patients with near or complete resolution of bony oedema and healing of any cortical defect, rehabilitation is focused on strength and conditioning and sport-specific exercise for the full return to activity. The length of this final stage is approximately nine weeks but depends on factors such as development and level of sports participation. If significant HSC remains on MRI, CT scan is considered to definitively assess cortical defect healing. For these patients, return to high-risk sports is delayed for up to three months. Chronic defects (2b and 3) cannot heal and are not braced, and rehabilitation follows traditional protocols. Conclusion: Appropriate clinical screening and imaging with MRI can identify pars pathology early. In those with potential for healing, we propose hard bracing and appropriate rehabilitation as part of a multidisciplinary management protocol. The validity of this protocol will be tested in future studies.

Keywords: adolescents, MRI classification, pars interticularis, treatment protocol

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Authors: Fani Sakellariadou, Danae Antivachis

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Purpose of this paper is to evaluate the environmental status of a coastal Mediterranean lake, named Koumoundourou, located in the northeastern coast of Elefsis Bay, in the western region of Attiki in Greece, 15 km far from Athens. It is preserved from ancient times having an important archaeological interest. Koumoundourou lake is also considered as a valuable wetland accommodating an abundant flora and fauna, with a variety of bird species including a few world’s threatened ones. Furthermore, it is a heavily modified lake, affected by various anthropogenic pollutant sources which provide industrial, urban and agricultural contaminants. The adjacent oil refineries and the military depot are the major pollution providers furnishing with crude oil spills and leaks. Moreover, the lake accepts a quantity of groundwater leachates from the major landfill of Athens. The environmental status of the lake results from the intensive land uses combined with the permeable lithology of the surrounding area and the existence of karstic springs which discharge calcareous mountains. Sediment samples were collected along the shoreline of the lake using a Van Veen grab stainless steel sampler. They were studied for the determination of the total metal content and the metal fractionation in geochemical phases as well as the characterization of the dissolved organic matter (DOM). These constituents have a significant role in the ecological consideration of the lake. Metals may be responsible for harmful environmental impacts. The metal partitioning offers comprehensive information for the origin, mode of occurrence, biological and physicochemical availability, mobilization and transport of metals. Moreover, DOM has a multifunctional importance interacting with inorganic and organic contaminants leading to biogeochemical and ecological effects. The samples were digested using microwave heating with a suitable laboratory microwave unit. For the total metal content, the samples were treated with a mixture of strong acids. Then, a sequential extraction procedure was applied for the removal of exchangeable, carbonate hosted, reducible, organic/sulphides and residual fractions. Metal content was determined by an ICP-MS (Perkin Elmer, ICP MASS Spectrophotometer NexION 350D). Furthermore, the DOM was removed via a gentle extraction procedure and then it was characterized by fluorescence spectroscopy using a Perkin-Elmer LS 55 luminescence spectrophotometer equipped with the WinLab 4.00.02 software for data processing (Agilent, Cary Eclipse Fluorescence). Mono dimensional emission, excitation, synchronous-scan excitation and total luminescence spectra were recorded for the classification of chromophoric units present in the aqueous extracts. Total metal concentrations were determined and compared with those of the Elefsis gulf sediments. Element partitioning showed the anthropogenic sources and the contaminant bioavailability. All fluorescence spectra, as well as humification indices, were evaluated in detail to find out the nature and origin of DOM. All the results were compared and interpreted to evaluate the environmental quality of Koumoundourou lake and the need for environmental management and protection.

Keywords: anthropogenic contaminant, dissolved organic matter, lake, metal, pollution

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Authors: Bahar Hazal Yalçınkaya, Bayram Yılmaz, Mustafa Özilgen

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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

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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

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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: 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: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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

Abstract:

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

Procedia PDF Downloads 73

Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

Abstract:

Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

Procedia PDF Downloads 122