Scientific Program
Day 1 :
- Neuroscience | Neuroimmunology | Neurosurgery | Neurophysiology
Session Introduction
Eduardo Jahn
Universidad Central de Venezuela, Venezuela
Title: Myasthenia gravis: Neurochemical and neuroimmunological bases of new therapeutic approach
Biography:
Contrary to the specialized view of medical practice, I consider rather the integration of internal medicine with basic sciences in the area of ​​neuropharmacology and neuroimmunology, which can be pointed out as relevant in my professional practice.
This integration allows a more complex and coherent vision of the way in which the different systems of the body are organized around a biological director little studied in medical schools: The Activating Reticular System (ARS)
The integration of knowledge allows a therapeutic approach aimed at addressing both the consequences of the disease and its causes or aggravating factors within the Autonomic Nervious System and the ARS.
I have participated in the development of new therapeutic designs for various conditions and diseases for two decades. I have contributed to research in international publications in the area of ​​neuropharmacology and neuroimmunology, integrated to the multidisciplinary group in the Institute of Experimental Medicine the UCV.
Abstract:
It is an autoimmune neuromuscular disorder that produces weakness and tendency to skeletal muscle fatigue; it consists of autoantibodies directed against acetylcholine receptors (AChR) in neuromuscular junctions. Weakness of bulbar innervation muscle groups can occur generating palpebral ptosis, diplopia, dysphagia, dyslalia, dyspnea, among other symptoms that accompany different degrees of generalized weakness. The usual treatment consists of the use of acetylcholinesterase inhibitors (Pyridostigmine), steroids and immunosuppressants, plasmapheresis, gamma globulins and timectomy, all of which can generate multiple complications.
Neurochemical findings, and immunological show low ratio NA / Ad, very high values ​​of plasma free serotonin (5Ht-l) and, an TH2 immunological profile, plus levels of anticolinoceptors that do not have a linear relationship with the intensity of the clinic.
We found that neurochemical findings yield with medication that increases neural but not adrenal norepinephrine by reversing not only the symptoms but also the TH2 profile. However, bulbar symptoms may return or not give very completely.
The nucleus A5 mainly gives the neural sympathetic activity (Na). A5 (NA) works in intense association with the Middle Rafe (MR), which in turn stimulates and regulates the cranial nerve nuclei. Thus, any pharmacological manipulation that favors the activation of MR improves the bulbar symptoms in MG.
In addition, the impact on the general condition of the patient due to pharmacological manipulations that decrease 5Ht-l are dramatic. Not only does 5Ht-l generate TH1 immunosuppression, it interferes with neuromuscular transmission but it also increases bronchial secretions, smooth muscle contraction and vagal activity, facilitating complications.
Through this therapeutic approach aimed at correcting neurochemical and neuroautonomic findings coupled with the experience of recent years, allow us to attend both generalized weakness and bulbar symptoms with a differential and complementary approach and adjusted to the individual therapeutic response. We thus avoid multiple complications given by the usual medication.
Nadine Touzeau
Net-profiler, researcher in behavior of cybercriminals, France
Title: Presentation of three scientific theories on the behavioral differentiations between the real and the virtual
Biography:
Nadine Touzeau is profiler, net-profiler and researcher in behavior of cybercriminals. Two scientific books "Net-profiling" (2015 and 2018) has become a reference in several research and teaching laboratories in the world. From November 2017 to today, she has published more than twelve scientific articles in American journals Behaviour Differentiations Between Real to Virtual Space and has revealed 4 theories about her research on Behaviour Differentiations Between Real to Virtual Space. She was a professor at Gendarmerie School at Madagascar and Criminology Institute in France and teach in a High School in Digital in Paris
Abstract:
It is by wanting to reproduce profiling as I practice it in the real world in the virtual world that my research work began. 4 theories have been revealed on several discoveries concerning "Behavioral Differentiations between the Real and the Virtual Space". Three of them will be presented to you during this conference: "Avatarization", "Transversal Zone" and "Virtual Intelligence".
These Behavioral Differentiations between the Real and the Virtual show that our behaviors evolve, change. They point out that the notion of time must be redefined, that some senses disappear because they are not used and that others could develop, that our physiognomy changes as well as our emotions and intelligences
Biography:
Carol Brown Ed.D., is in expert in the field of clinically applied neuroscience. She developed the Equipping Minds Cognitive Development Curriculum which is used in educational, home, clinical, and vocational settings with individuals of all ages with neurodevelopmental disorders. She has seen increases in verbal and nonverbal abilities, working memory, processing, fluid reasoning, language, academics, and intelligence quotients. The Brown 9 n-back uses letters, numbers, colors, sounds, images, and directions to strengthen neuropathways to build cognitive functions.
Abstract:
The Equipping Minds Cognitive Development Curriculum (EMCDC), a holistic cognitive intervention program, is based on the theory of Structural Cognitive Modifiability (SCL) and Mediated Learning Experience (MLE) of Reuven Feuerstein. EMCDC has been applied with learners of all ages with learning and neurodevelopmental disabilities in the United States and internationally. Five case studies of learners with a neurodevelopmental disorder are presented. Brown utilized the following data collection techniques: clinical observations of the leaners, examining and analyzing the psychological and educational documents, and interviewing the parents, the leaners, and teachers. Cognitive and academic gains were demonstrated in all of the case studies. The results are consistent with the results of Brown’s doctoral research with learners with a Specific Learning Disorder and the four -year case study with Marie who had Down syndrome. Family members, therapists, and teachers were included in the therapy sessions and instructed how to interact and instruct using mediated learning. This suggests that a comprehensive intervention program which addresses numerous cognitive functions and includes parents and other professionals in the learner’s life allows more opportunities for modification. J Altern Med Res 2018;10(2) 171-193
Vasily V Vlasyuk
S. M. Kirov Military Medical Academy, Russia
Title: Configuration (molding) of the skull and birth trauma
Biography:
Vasily V. Vlasyuk is the doctor of medical Sciences, Professor, Academician of the European Academy of Natural Sciences, Academician of the International Academy of inventions and discoveries. Now he works as Expert Department of forensic medicine of the S. M. Kirov Military Medical Academy, Saint-Petersburg. After graduating from the Leningrad Pediatric Institute he is worked 1n the Institute of Perinatal Medicine, Obstetrics and Gynecology, Neurosurgical Institute in St. Petersburg, Head of the Laboratory of morphology in the Institute of mycoses, Children's Hospital name K.A.Rauhfus, Head of Department Institute of Childhood Infections and others. He has worked in Mongolia as an expert WHO on child mortality. His major research interests in the pathology of the central nervous system in fetuses and newborns, birth injury, intracranial hemorrhages, childhood infections, immunohistochemistry. Make scientific discoveries about the correlation between changes in the skull and damage to the cerebellar tentorium
Abstract:
Configuration is an evolutionarily formed process that ensures the adaptation of the size and shape of the head to the birth canal of the mother, and also prevents birth injury to the mother and fetus. The configuration can be physiological and pathological. The pathological configuration is accompanied by birth mechanical damage, and the physiological - no, prevents birth trauma (BT). The pathological configuration is divided into 1) excessive, 2) rapid and 3) asymmetrical [1]. Three degrees of configuration can be distinguished [12] - 1) light, 2) moderate and 3) pronounced. 1 degree - bones overlapping along one of the sutures, 2 degree - bones overlapping within 2-3 sutures, 3 degree - bones overlapping at 4-5 sutures. Clinical and experimental studies have shown that head compression leads to deceleration of cardiac activity. The pathological configuration leads to both birth trauma (BT) and compression hypoxia (CH) of the brain. In BT, pronounced mechanical damage dominates in the form of ruptures of TC, falx, bridging veins, fractures, large focal subarachnoid and intracerebral hemorrhages, subdural hemorrhages, etc. In CH, hypoxic damage to the brain caused by impaired blood circulation, venous congestion, increased intracranial pressure, compression of the blood vessels of the brain, and others dominate: spotted subpial hemorrhages at the apex of the convolutions, subarachnoid hemorrhages in areas of the cerebral hemispheres where bridging veins connect with the arachnoid membrane, hemorrhages in the region of the quadrangular lobes of the cerebellum, etc. When studying the skull, a connection was found between asynclitism and damage (rupture, hemorrhage) of the tentorium cerebelli. Studying the configuration of the fetal head during childbirth can help in the diagnosis and prevention of BT and CH.
Olga Zinovyeva
Sechenov First State Medical University, Russia
Title: Muscle Atrophy in Women with Chronic Alcoholic Myopathy
Biography:
Zinovyeva is a Professor of the Department of nervous diseases Sechenov First State Medical University, Moscow, Russia. Together with specialists radiologists, morphologists, pathophysiologists conducted studies of the mechanisms of injury of the peripheral nerves and skeletal muscles in patients with chronic alcohol intoxication. The algorithm for diagnosing chronic alcoholic myopathy has been developed. A search is conducted for pathogenetically substantiated methods of treating neurological manifestations of alcoholic illness. Research in this area is of great scientific and socio-economic importance.
Abstract:
Statement of the Problem: Chronic alcoholic myopathy (CAM) is observed in 40–60% of patients with chronic alcoholic intoxication. The majority of studies have been performed in male patients; therefore, sex-related differences in the development of atrophic changes in CAM in women have not been investigated. The purpose of this study was to compare morphological changes in lower limb muscles in female patients with a current history of alcohol abuse using magnetic resonance imaging (MRI) and immune histochemical morphometric tests of biopsy specimens. Methodology & Theoretical Orientation: The study included eight female patients with alcohol abuse. The mean age of patients was 44.8 ± 1.9 years; the mean duration of alcohol abuse was 7.1 ± 1.3 years; the daily dose of ethanol was 12.3 ± 1.7 units. The control group included 15 female volunteers of the same age with no history of alcohol abuse. All patients and volunteers underwent clinical examination in order to rule out concomitant disorders. All patients and eight volunteers underwent MRI examination of hip muscles. We also performed the biopsy of m. quadriceps femoris vastus lateralis in five patients. The clinical signs of myopathy were observed in five (62.5%) patients. MRI examination showed that the volume of m. quadriceps femoris in the group of patients was significantly decreased. The immune histochemical morphometric analysis of m. vastus lateralis specimens showed, that the mean cross-sectional area (CSA) of both type I and type II muscle fibers in the group of patients is decreased (Table 1). Conclusion & Significance: this is the first study to observe the atrophy of m. quadriceps femoris and a decrease in the size of type I and II muscle fibers in women with chronic alcoholic intoxication
Table 1. Cross-sectional area (μm2) of muscle fibers in patients with chronic alcoholic intoxication and healthy controls.
|
Parameters |
Groups |
|
|
control (n = 7) |
patients (n = 5) |
|
|
CSA of type I muscle fibers CSA of type II muscle fibers |
4802 ± 128 4498 ± 132 |
3353 ± 189* 2529 ± 310* |
* Significant differences, p < 0.05.
Isaac Levi
MD Biosciences Ltd, Israel
Title: BBB Disruption and Permeability of Brain Tissues in MBP Induced Experimental Autoimmune Encephalomyelitis (EAE) Model in Rats
Biography:
Dr. Levi is the pre-Clinical department manager at MD Biosciences Ltd. MD Biosciences is a global industry-leading provider of preclinical services include efficacy and mode of action studies in the inflammation, immunology and CNS therapeutics areas. Dr. Levi holds a Ph.D. in Medical Science from the department of Immunology and Microbiology, Faculty of Medicine, in Ben Gurion University, Israel
Abstract:
In spite of differences between the pathophysiology of EAE and the human Multiple Sclerosis (MS), EAE has become a common animal model in the development therapies for treatment of MS. The Myelin Basic Protein (MBP) induced EAE in rat consists of inflammatory cells infiltration into the spinal cord, cerebellum and brainstem. The paralytic episodes that in this model are thought to be the result of blood–brain barrier breakdown, inflammation, and edema, but not from demyelination. This paralysis initiates approximately 10 days post induction, followed by spontaneously recovers in 5–7 days. Therefore, the therapeutic window is very short. Blood-brain barrier (BBB) disruption and permeability in MBP-EAE animals was assessed by culling animals on study days 2, 6, 9, 11 and 13 for brain harvest, 2 hours following an intrajugular injection of 4% Evan’s blue solution. Following collection, brains were sliced and immersed in formamide at 55°C overnight to extract the Evan’s blue dye. The Evans blue dye content was quantified as μg/g brain tissue. Our data show that while the first clinical signs of the disease were seen on study day 9 following induction with MBP, the Evan’s blue dye was observed in the brain already 2 days following induction (17.80±3.29 μg/g). The dye content in the brain tissue remained high until study day 9 (18.40±2.16 μg/g). Its level markedly decreased on study day 11, and was similar to the level in the naïve brain tissue Mono-nuclear and T-cells infiltration to the brain was observed early following induction with MBP, before the initiation of the first clinical symptoms of the disease. These data show dissociation between BBB permeability and the pick of the disease questioning the therapeutic vs. prophylactic traditional approach.
Elisabeth TM van der Gulik
Radboud University, Netherlands
Title: The situation of patients and the medical health care in future
Biography:
Elisabeth van der Gulik has followed an career as a medical doctor, in which she developed a great interest in pathologic anatomy. She was active in hospitals in Amsterdam, Brussel, Paris, as assistant pathologist and researcher. One of the topics in her research was the reaction of astrocytes in the environment of intracerebral lymphomas, metastatic lymph nodes without primary origin. Since 1992 she was active as physician in social medicine, assessment, assurance medicine, till she became a position as physician in different arbo services of occupational health. She retired since 2012 and wrote two books, both in Dutch/English with as title: Het Verzuimgesprek/The Absenteeism and De Toepasbaarheid van Enkele Stressmodellen en de relatie met verander- en stressmanagement in de werksituatie/ The Applicability of several stress models and the relation to Change- and Stress management in the Working Situation
Abstract:
New contributions to the development of health care give a different look to the place of the patient. It appears, that the outcome of medical treatments may depend of the specific medical and physiological condition of the patient and even other kind of conditions outside the patient may contribute to the results of the whole of medical treatment. New entities as effectiveness, participation of the patient, ethics, technics, digitization, multidisciplinary approach of research and consultation, deliver a total different look to the way as to how health care has to be secured. New specializations in medical law, medical management, tend to be developed day by day. New specializations of medicine will bring more effectiveness in using medical procedures. For example, Translational Medicine tends to find the best effective way of setting up new treatments, new scientific investigations. The introduction of Personalized, Predictive and Preventive Medicine, the Translational Medicine and Precision Medicine, will enhance the implementation of scientific findings. Every contribution in this development have to consider the effect to the final result in the health care system. The importance of the condition of the patient remains always the leading motive.
Albert Mensah
Mensah Medical, USA
Title: Nutrient Imbalances Versus Mental Health - A New, All-Natural Paradigm: Test - Treat - Improve
Biography:
Abstract:
Synopsis: Mensah Medical is an internationally renowned clinic that specializes in the treatment of biochemical imbalances, and the cognitive (and physical) disorders caused by those imbalances. Founded in 2008, Mensah Medical treats thousands of patients each year using targeted nutrient therapy, an all-natural, non-pharmaceutical approach to addressing the imbalances that lead to mental and psychological conditions such as ADD/ADHD, Autism, Anxiety, Depression, Behavioral Disorders, Bi-polar Disorder, Eating Disorders, Schizophrenia, Alzheimer’s Disease, and several others. Many of the treatment protocols utilized at Mensah Medical are based on decades of research conducted by mental health treatment pioneers such as Dr. Carl Pfeiffer and Dr. William Walsh. Mensah Medical puts these protocols into medical practice, further validating the effectiveness of nutrient therapy and identifying new and improved applications for natural, biochemical balance treatment protocols.
Evidence demonstrates that mental and psychological conditions are often misdiagnosed and/or underdiagnosed. For example, children are often mislabeled as having Behavioral Disorders or ADD/ADHD when, in most cases, they are simply undernourished or experiencing easily addressed biochemical imbalances. Adolescents and teens struggle needlessly with depression, anxiety, and mood dysregulation when simple tests and treatments for excessive krypto-pyrroles could lead to significant reduction, if not elimination, of their symptoms. Several adult patients face mental/psychological disorder diagnoses and are told that their symptoms can only be managed rather than cured, yet simply addressing the biochemical imbalances that are the root cause of these symptoms can lead to significant improvement.
Learning Objectives: 1) What biochemical imbalances (i.e. pyrrole disorder, over or under methylation, insufficient zinc, excess copper) correlate with specific mental and psychological disorder symptoms? 2) What evidence demonstrates the efficacy of nutrient therapy in addressing and resolving mental and psychological disorders? 3) What are some cross-functional physical health benefits of nutrient therapy that go beyond mental health applications (i.e. cardiovascular health, strengthening of the immune system, improved e
Fabiola M. Ribeiro
Universidade Federal de Minas Gerais (UFMG) Brazil
Title: Preventing ZIKV-induced microcephaly: The pros and cons of classic and newly developed drugs
Biography:
Abstract:
During the Zika virus (ZIKV) outbreak in Brazil (2015-2016), more than 4,500 cases of newborns exhibiting microcephaly have emerged. Soon after that, the relationship between ZIKV and microcephaly was clarified, as it was shown that the virus was present in the brain of microcephalic fetuses. Moreover, studies published by our group show that ZIKV is able to infect and rapidly multiply in murine neurons, triggering the release of glutamate and inflammatory cytokines. Interestingly, blockade of the glutamate receptor, N-methyl-D-aspartate receptor (NMDAR), with memantine prevents ZIKV-induced neuroinflammation and neurodegeneration both in vitro and in vivo. Memantine has been used for several years to treat patients and is considered safe by the Food and Drug Administration (FDA) to treat pregnant women (Pregnancy drug category B). However, virus replication was not affected by memantine. Interestingly, a newly developed antiviral drug was also tested by our group, showing very promising results in terms of decreasing ZIKV replication. Although this antiviral drug could be an interesting therapeutic option, there are several difficulties for the conduction of clinical trial studies to test new drugs to treat pregnant women and their fetuses. Therefore, drug repositioning, as it is the case of memantine, could be a safer option. We propose that antiviral and neuroprotective drugs, in combination or separately, could be an effective therapeutic strategy to prevent ZIKV-induced congenital syndrome. Currently, we are testing these drugs in an embryonic mouse model of ZIKV infection.
Diana Marcela Cuestas Torres
Universidad de los Andes, Colombia
Title: Evaluation of the spontaneous activity of hippocampal neurons exposed to different concentrations of beta-amyloid (Aβ)
Biography:
Marcela Cuestas, from her beginnings as a scientist, has had a great interest in the cellular mechanisms behind the processes of synaptic plasticity related to the formation of memory and learning. Since one of the characteristic features of Alzheimer's disease (AD) is the deterioration of cognitive processes and that, the processes of synaptic plasticity underlie these. She and her group of collaborators decided to evaluate how the synaptic activity of hippocampal neurons changes in Alzheimer's models. Therefore, he has extensive experience in the electrophysiological evaluation of neuronal activity in vivo and in vitro using patch clamping techniques and field registration in Alzheimer's models. Its field of action seeks to contribute, both to the diagnosis of AD, through the typing of patterns of spontaneous synaptic activity; as to the treatment of AD, by identifying new therapeutic targets to mitigate the harmful effects of beta-amyloid accumulation on cognitive function. She hopes to continue making important contributions to the basic knowledge related to the disease and clinical application. As well as continuing to promote the development of Alzheimer's neurophysiology in Colombia.
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disorder related to age and characterized by producing a cognitive deficit, specifically memory loss, and deterioration of learning processes. One of the main features of AD is the extracellular accumulation of beta-amyloid (Aβ), which can form beta-amyloid oligomers (AβO). These AβO applied ex vivo and in vivo act on the mechanisms underlying the learning processes, such as long-term depression (LTD) and long-term potentiation (LTP); facilitating the first (1,2) and deteriorating the second (3,4). In spite of the recent findings that relate the alterations of the neuronal synaptic activity with the deterioration of the cognitive processes, characteristic of AD; there is little or nothing that is known about the synaptic cellular mechanisms that would explain this detriment. Given the determinant role of spontaneous activity in the maturation and maintenance of synapses, homeostasis, and plasticity (5,6,7), it is critical and interesting to study how it changes This type of basal activity in primary culture of hippocampal neurons exposed to different concentrations of AβO. Specifically, how the probability of release of neurotransmitters changes, the sensitivity of postsynaptic receptors, the expression of new postsynaptic receptors and the flow of current through these receptors. In the present work, we applied different concentrations of oligomeric beta-amyloid (AβO) on primary cultures of hippocampal neurons of rat embryos, followed by evaluation of spontaneous electrical activity, specifically excitatory postsynaptic potentials sEPSP through the patch clamp technique whole-cell mode, finding changes in amplitude and frequency of the sEPSP. Understand the effects of AβO on sEPSP, crucial for neuronal functioning and communication; it will allow us to elucidate the synaptic cellular bases behind the cognitive deterioration characteristic of AD, which will facilitate the typing of sEPSP patterns that contribute to improving the diagnosis of AD; as well as, the identification of new therapeutic targets that mitigate the deleterious effects of AβO on cognitive function.
Yesim Kaya
Mugla Sitki Kocman University, Turkey
Title: Speedy/RINGO as a neuroprotector in neurodegeneration
Biography:
She works as a Research Assistant in Mugla Sitki Kocman University at Molecular Biology and Genetics Department. She completed two master’s education. She has studied about “identifying the role of Speedy/RINGO on MAPK and AKT pathways intersection in neuroblastoma cells” during her second master education.
Abstract:
Statement of the Problem: Neurodegeneration is the progressive loss of function and structure of neurons that cause neuronal cell death. Although neurodegeneration is a multifactorial process, one of the main causative factors is elevated intracellular calcium levels which leads to apoptosis by inducing p53, thus negatively affecting two pathways: mitogenic extracellular signal-regulated kinase/mitogen activated protein kinase(ERK/MAPK) and survival phosphoinositide 3-kinase/protein kinaseB(PI3K/AKT) pathways. Speedy/rapid inducer of G2/M progression in oocytes (Speedy/RINGO) is a cell cycle regulatory protein that increases survival of p53-positive mitotic cells by inhibiting the apoptosis. Moreover, we showed for the first time that this protein elicits p53-dependent anti-apoptotic effects in calcium-induced degenerated primary hippocampal neurons. Methodology&Theoretical Orientation: Our laboratory is currently investigating whether Speedy/RINGO exerts this anti-apoptotic function through ERK/MAPK and PI3K/AKT pathways. For this purpose, we used undifferentiated p53 and Speedy/RINGO-expressing neuronal-like neuroblastoma cells as preliminary model. Findings: Our previous investigations indicated that Speedy/RINGO protects neurons against calcium-mediated p53-dependent apoptosis without decreasing p53 levels. This finding implies that the anti-apoptotic effect of Speedy/RINGO is downstream of p53 activation, not directly on p53 itself. The most remarkable downstream targets of p53, in terms of generating an apoptotic effect on neurons, are ERK/MAPK and PI3K/AKT pathways. Within this context, silencing of the Speedy/RINGO gene significantly alters expression levels and phosphorylation states of certain members of these pathways. This leads to apoptotic death of neuroblastoma cells, likely due to the absence of Speedy/RINGO’s regulatory function on these two pathways. Conclusion & Significance: Preliminary data indicates that Speedy/RINGO plays an essential role on the regulation of ERK/MAPK and PI3K/AKT pathways that directly affect the apoptotic state and survival rate of cells giving insights about molecular mechanism of Speedy/RINGO in neuronal survival. However, to understand the exact mechanism of Speedy/RINGO’s anti-apoptotic function in neurons, studies is being performed in our laboratory both with in vitro degenerated primary neuron models.
Suelen Baggio
Federal University of Rio Grande do Sul, Brazil
Title: Glutamatergic neurotransmission system is impaired in an adult zebrafish FASD model
Biography:
I am a Biologyst and PhD. student of Biochemistry in Brazil. My research involves brain glutamatergic system impairment on an adult zebrafish FASD model. My goal is to increase our understanding in the alterations of neurochemical functions in the glutamatergic system, in an addition to an attempt to modulate these impairments observed FASD with pharmacological modulation. I study this model since 2014, which resulted in two publications as first author: Embryonic alcohol exposure promotes long-term effects on cerebral glutamate transport of adult zebrafish (Neuroscience Letters, 2017), and Embryonic alcohol exposure leading to social avoidance and altered anxiety responses in adult zebrafish (Behavioral Brain Research, 2018).
Abstract:
Background: Fetal Alcohol Spectrum Disorder (FASD) is a syndrome related to ethanol (EtOH) exposure during development with neurological impairment. Glutamatergic neurotransmission is modulated by EtOH exposure, which affects synaptic plasticity and cognitive processes. Adult zebrafish is a known model to evaluate long-lasting impairments of milder forms of FASD, also used to investigate the glutamatergic system. Aim: Evaluate brain glutamatergic system of adult zebrafish exposed to ethanol during development. Methods: zebrafish larvae (24 h post-fertilization), were exposure to EtOH (0.0%, 0.1%, 0.25%, 0.5% and 1%) for 2 hours. After 4 months, the animals were euthanized and their role brain was used to access: glutamate transport uptake activity; glutamate binding in enriched membrane fraction; glutamine synthetase (GS) activity; Na+/K+ ATPase activity; and high-resolution respirometry. Results: Animals exposed to EtOH 0.5% and 1% presented a 50% reduction of brain glutamate uptake compared to control (p < 0,001). Ceftriaxone, a positive modulator of glutamate uptake, rescued 50% of this drop (p < 0,0001). Both groups presented reduced levels of glutamate binding compared to control (43% and 60%, respectively, p = 0,0041). Both groups presented 32% reduction in Na+/K+ ATPase activity compared to control (p = 0,0003). One-fifth of GS activity was reduced on EtOH 1% group compared to control (p = 0,0032). No alterations were observed in high-resolution respirometry. Conclusion: Embryonic alcohol exposure disrupts adult zebrafish glutamatergic neurotransmitter system
Nataliia O. Melnyk
National O.O.Bogomolets medical university, Ukraine
Title: Influence of Interferon beta-1a on Neurons of Central Nervous System and Immune Organs after Initiation of Demyelination and Remyelination
Biography:
Nataliia O. Melnyk - the Professor of the Histology and Embryology Department of National O.O.Bogomolets Medical University, the Main Scientist in the Institute of Genetic and Regenerative Medicine National Academy of Medical Sciences of Ukraine, Kyiv. Graduated from Kyiv National Taras Shevchenko University in 1993, after an assignment she worked as an engineer in the Institute of Molecular Biology and Genetics. During 2008- 2011, she worked as Deputy Head of the Department of Education and Methodology of the National O.O. Bogomolets Medical University. She has more than 380 scientific and methodological works, 5 patents of scientific research. Nataliia Melnyk was edited base textbook of Histology, Cytology and Embryology for students of medical universities in Ukraine and Atlas of Histology, Cytology and Embryology for students of medical universities in Ukraine
Abstract:
In experimental work was investigate morphological changers of neurons and myelinated nerve fibers in organs of central nervous system (CNS), organs of immune system - thymus and spleen, after initiation of experimental model of demyelination and remyelination.
The model of demyelination - EAE (experimental allergic encephalomyelitis) in rats, was use to investigation of changers of neurons in cortex of cerebrum, cerebellum and spinal cord on 21 days and 39 days. After staining of histological sections of the brain and spinal cord by toluidine blue and cresyl violet, we observed the percentage of neurons with unmodified, moderate and severe structural changes. We studied of demyelination process of nervous fibers in organs of CNS by the methods of electron microscopy and morphometry. After influence of Rebif® (interferon beta-1a) by 2 weeks, we observed of remyelination process - the percentage of normal neurons in the brain and spinal cord was increased, the amounts of neurons with severe and destructive changes were reduce and myelinated nerve fibers was regenerate.
In thymus and spleen was observe structure changes – formation large nodules in spleen, activations of thymus – formation of small nodules in cortical parts of lobules. Was observe correlations between structural changes in organs of CNS and organs of immune system.
Day 2 :
- Neuroscience | Neuroimmunology | Neurosurgery | Neurology | Neuropsychiatry and Behavioural Science
Session Introduction
Veronika E. Neubrand
University of Granada, Spain
Title: The atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia
Biography:
Veronika Neubrand possesses a Biology degree from the University of Heidelberg and a PhD from the European Molecular Biology Laboratory (EMBL) and the University of Heidelberg, Germany. Currently she holds an associate professorship at the department of Cell Biology at the University of Granada, Spain.
In 2009 at the IPBLN-CSIC, Granada, Spain, she started to study the cell biology of microglia, the immune cells of the brain, which play an essential role in neuroinflammation, an important hallmark of neurodegenerative diseases, such as Alzheimer´s and Parkinson´s. In 2014, she was awarded a research grant by the Michael J Fox Foundation, USA. As principle investigator of this grant she identified molecules involved in the generation of CNS-supporting microglia, which represent drug targets for the diseases mentioned above. From 2005 to 2009, Veronika investigated the molecular mechanisms of axonal and dendritic growth in neurons at the Cancer Research UK London Research Institute.
Abstract:
Over-activated microglia, the resident immune cells of the brain, play a central role during neuroinflammation, leading to neuronal cell death and neurodegeneration, for example in Alzheimer´s and Parkinson´s disease. Reversion of these over-activated microglia to a neuroprotective phenotype could regenerate a healthy Central Nervous System (CNS)-supporting microglial environment. Our aim was to identify a dataset of intracellular molecules in primary microglia that play a role in the transition of a neurotoxic phenotype to a ramified, neuroprotective one. To do this, we exploited the anti-inflammatory and neuroprotective properties of conditioned medium of adipose-derived mesenchymal stem cells (CM) as a tool to generate the neuroprotective phenotype of microglia in vitro, and we set up a microscopy-based siRNA screen to identify its hits by cell morphology.
We assayed an siRNA array targeting more than 150 genes that codify proteins of cytoskeleton and inflammatory pathways in microglia. From them, siRNA-downregulation of more than 40 genes significantly inhibited the CM-induced transition from a neurotoxic to a neuroprotective microglia phenotype, and 50 siRNA-downregulated genes had the opposite effect. As a proof-of-concept, seven of these targets were validated by downregulation of protein expression with individual siRNAs. They were assayed in functional screens that revealed that the atypical RhoGTPase RhoE/Rnd3 is necessary for BDNF expression and plays an essential role in controlling microglial migration.
Besides the identification of RhoE/Rnd3 as a novel inducer of a neuroprotective phenotype in microglia, we propose a list of potential targets to be further confirmed with selective activators or inhibitors.
Acknowledgements: This work was supported by a Michael J Fox Foundation research grant.
Alexey Boyko
Pirogov Russian National Research Medical University, Russia
Title: Approaches to immunomodulation in relapsing multiple sclerosis
Biography:
Alexei Boyko gained his MD and PhD from the Russian State Medical University, Moscow and has been Professor of the Department of Neurology and Neurosurgery at this university since 1997. He was the Chief Neurologist of the Department of Health Care of the Government of Moscow in 2001-2015, Director of the Moscow Multiple Sclerosis Center in 2004-2014 and Director of the MS Clinical and Research Center of Neuroclinic since 2015, Director of the Neuroimmunological Department of the Federal Center CVPS. Professor Boyko has been a member of the "Oslo International Think-tank on MS Epidemiology, Analytical Approaches to Study of the Aetiology" at the Center for Advanced Studies of the Norwegian Academy of Science and Letters in 1994-1995, and worked at UBC MS Center in 1998 (Vancouver, Canada). He is also a member of the Presidium of the All-Russian Society of Neurologists, Co-ordinator of the Medical Consulting Boards of Moscow and All-Russian MS Societies, President of RUCTRIMS, member of ECTRIMS Council
Abstract:
The BCD-132 and BCD-054 (JSC BIOCAD, Russia) are novel immunomodulating therapeutic options for relapsing form of multiple sclerosis (MS) treatment.
The BCD-054 is a conjugate of recombinant human interferon β1a and linear polyethylene glycol (PEG) with a molecular weight of 30kDA. Such conjugation decreases renal clearance, increases half-life of drug and, consequently, allows to prolong the duration of action and reduce the frequency of injections compared with non-pegylated forms of interferon.
The interim 20-week results of BCD-054 III phase study showed significant reduction in brain MRI disease activity on PEG interferon β1a therapy compared with placebo. It was proven, what two studied doses of BCD-054 superior to placebo for the primary efficacy endpoint represented by combined unique active (CUA) lesion counts. Assessment of clinical performance demonstrated the reduction of relapse rate: BCD-054 180 μg - 10, 62%, BCD-054 240 μg - 6,14%, low dose interferon β1a (LIB) - 15,93%, placebo - 15,79%.
Another potential treatment of MS is BCD-132, an innovative the 3rd generation humanized afukosylated anti-CD20 antibodies. It has increased affinity for FcγRllla, thereby effectively induces antibody-dependent cytotoxicity and antibody dependent phagocytosis.
Direct strictly specific effect of BCD-132 on B lymphocyte in a wide range of doses (100-1000 mg) was established by dynamic assessment of such cells lever in phase I clinical trial after intravenous administration of increasing doses in two dosage regimens.
The obtained data shows that BCD-132 has an expected pharmacodynamic effect of long-term depletion of CD19+ and CD20+ B cell lineage and an acceptable safety profile when used to treat patients with MS in all studied doses.
Biography:
Guru Prasanna Lakshmi has her expertise in Neuropsychology and Psych oncology, she goes through a client centered approach, where she designs the curriculum in holistic manner. Her research is based on neuropsychological issues in Cancer patients and in the area of Dementia. Her practically approached research Is further imbibed in the interventions.
Abstract:
Cancer as a condition, primarily focused on treating the disease per se, as extensive literature suggests a link between cognitive dysfunction and cancer related treatment (Chemotherapy, Radiotherapy, Hormone Therapy). But the literature is limited is limited in terms of cognitive dysfunction related to cancer itself. Psychological distress in various types of cancer has been proved by previous studies. Still the research relating cognitive inflexibility with psychological distress is very much limited.
Aim and method: The aim of the present research is to study the levels of cognitive flexibility, functioning and to explore the role of the cognitive inflexibility in causing psychological distress among various types of cancer patients. A sample of 75 various types of cancer patients were assessed using neuropsychological tool WCST, psychological tools Distress Thermometer and Rating scale, HAM-A, and HDRS.
Results: the study findings showing significant levels of distress, anxiety, depression, and cognitive inflexibility among various types of cancer patients. There was a significant positive and negative correlation between WCST scores of most of the categories with distress variable scores and anxiety scores respectively. No significant correlation was found between the depression scale scores with WCST scores. Predictor variables of cognitive inflexibility in causing psychological distress were significant with the socio demographic and clinical characteristics of the participants.
Conclusion: Symptom management and qualify of life are an essential part of survivorship. The psychological and neuropsychological investigation should include as an adjuvant to cancer treatment.
Key words: Cancer, Cognitive inflexibility, Psychological Distress, Depression, and Anxiety.
Michael R. Yeaman
David Geffen School of Medicine at UCLA, USA
Title: The Phenomenal Story of Neuromyelitis Optica Spectrum Disorder: Neurological Autoimmune Mystery to Functional Cure at the Speed of Life
Biography:
Michael Yeaman is a tenured Professor of Medicine at the University of California, Los Angeles, Vice Chair of Medicine and Chief of Molecular Medicine at Harbor-UCLA Medical Center. He studies antibiotic-resistant infections & immunology of autoimmune diseases. He is Chair Medical Advisor, Guthy-Jackson Charitable Foundation in its mission to cure neuromyelitis optica. He received the National Research Service Award (NIH), Innovation Award (NIH) and Distinguished Investigator Award (U.S. Department of Defense). He has published >200 scholarly works and holds 27 issued patents. He co-authored the acclaimed book The Power of Rare, a blueprint for solving rare diseases. He founded NovaDigm Therapeutics, Inc. and Metacin, Inc., lectures internationally and serves on editorial boards of premier medical journals. Michael is an accomplished musical composer and performer integrating art, science and medicine for health & wellness. His music appears in films & multimedia, his 15 albums are available on iTunes® and Spotify®, and his Pandora® radio station is part of the music genome
Abstract:
Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that manifests via inflammation and demyelination typically targeting optic nerves & spinal cord. Patients often experience a relapsing course of cumulative neurological debility. Latest epidemiologic data suggest hundreds of thousands of cases worldwide, many of which remain undiagnosed and ineffectively treated. Despite its potential for devastating and irreversible neurologic disabilities, no treatment had been proven safe and effective in prospective, masked and adequately powered clinical trials in over a century.
Key Advances: Integration of innovative molecular and cellular immunology, epidemiology, clinical characterization & treatment effects clearly differentiate NMOSD from multiple sclerosis (MS). Once viewed as solely B-cell driven, autoreactive T cells and loss of immune tolerance to aquaporin-4 or other autoantigens are now recognized as crucial to NMOSD immunopathogenesis. Four phase IIb/III clinical trials have now reported positive findings in evaluating three drugs (eculizumab, inebilizumab, satralizumab) for safety and efficacy to delay or prevent relapses in NMOSD. In 2019, the first of these drugs received regulatory approval having achieved >98% relapse-free efficacy among patients on drug in the trial period. The other agents are now in regulatory review.
Prospectus: In just a single decade, The Guthy-Jackson Charitable Foundation has led a phenomenal story of research innovation, patient advocacy and industry synergy to revolutionize the field and provide a promising future for NMOSD patients. Significant next steps include identifying predictive biomarkers of relapse and restoring immune tolerance for cures to spare patients from cancer and infectious disease risk of lifelong immunosuppressive therapy. Preventative research areas include etiology, genetic or environmental risk factors & epidemiologic correlates of disease course or severity. Scientific and therapeutic breakthroughs in NMOSD will benefit patients with other autoimmune diseases.
Sara Dehbashi
Thomas Jefferson University, USA
Title: Co-occurrence of multiple sclerosis and myasthenia gravis: A case report and review of immunological theories
Biography:
Sara Dehbashi obtained her medical degree in Shiraz, Iran. She started her medical experience in United States as a research fellow in Washington University in St. Louis working in an immunology lab. She completed her neurology residency training in University of Texas Medical Branch and MD Anderson Cancer center, and her Fellowship in Neuromuscular Medicine in Icahn School of medicine at Mount Sinai in New York. She is currently working as Assistant Professor of neurology in Thomas Jefferson University, and is enthusiastic about teaching medical students, residents, fellows, and research in addition to her clinical duties.
Abstract:
Autoimmune mechanisms are implicated in both myasthenia gravis (MG) and multiple sclerosis (MS), and hypothesis of a common immunological mechanism of pathogenesis is supported by the fact that this rare combination of the two diseases occurs more frequently than expected by random association. Although MS is primarily mediated by T lymphocytes and MG primarily involves the destruction of the neuromuscular junction by antibodies, there are evidences that support both cell-mediated and humoral immunity are involved in the pathogenesis of both diseases. Different studies have shown dysfunction of T cells as well as B cells involved in the pathogenesis of both disorders. Previous case reports, mainly present female patients who had a mild presentation of MG, either prior or after diagnosis of MS. In this article, in addition to presenting a unique male patient with a previous diagnosis of MS, who presented with MG crisis, we aimed to review the literature to find the common immunological mechanisms involved in the pathogenesis of MG and MS.
Leigh Richardson
Brain Performance Center, USA
Title: Trauma and the Body; Leaving it’s Mark on a Neurobiological Level
Biography:
In 2009 Leigh opened the Brain Performance Center offering a wide array of treatment options, neurotherapy, neurostimulation and CBT for many neurological issues. In the last 15 years Leigh has observed trauma on all levels, at all ages. This lead to her obtaining a Trauma Certification, CCTP I and II. Leigh is the author of Turn Your Brain On, Get Your Game On, an international speaker, and regular contributor to FOX news as a brain health expert. She is the Clinical Director of the Brain Performance Center.
Abstract:
About 8 million people suffer from PTSD during a given year. Psychological trauma is the unique individual experience of an event, a series of events, or set of enduring conditions in which the individual experiences a threat to life, bodily integrity, or sanity. After the threat has passed, the trauma lives on as an emotional memory in the body and brain, and converts the past into an expectation of the future. Not understanding trauma, individuals identify and connect to the emotion.
Trauma survivors remember the event through their senses, what they saw, felt, heard, smelt, and tasted. These sensory elements become implicit memories, automatic or unconscious. The human body is self-protective and the brain is biased to respond to any danger signal it has known before. When something happens, they are triggered, and can’t prioritize the past from the present. They shut down.
Neuroscience has offered new theories about how the brain processes traumatic experiences. A recent important finding has shown that the frontal lobes which are responsible for higher level thinking area, become less active under stress, and the body goes into an emergency stress response. Our sympathetic nervous system takes over and puts us in the fight or flight mode. This state of hyperarousal causes the adrenal glands to release cortisol, which triggers the parasympathetic nervous system that has a freeze-submit mode.
To address the somatic legacy of trauma, we must first discover how the body has remembered the trauma, and then utilize somatic experiences needed for resolution. The therapy is less focused on what happened then and more focused on understanding the habits of response; too much or too little affect, movement or stillness, and helping the client to stay in the present. Regulation of arousal is the foundation for successful treatment, and keeping the frontal lobes “online” is a priority. Mindfulness is one of the tools used to discover and transform how the client organizes thoughts around the event.
Julianne Freiwald-Gaule
Vero Beach Reading and Speech-Language Pathology, USA
Title: Neuroscience and its application to the field of pediatric speech-language pathology
Biography:
Julianne Freiwald has been practicing in the field of speech-language pathology for close to 40 years. She received her undergraduate degree in speech and hearing sciences from the University of Miami in 1980. She received her masters and doctoral degrees from Nova Southeastern University in Speech-language pathology. Her interest in neuroscience peaked when she completed the course, “The Neurology of Behavior” at Harvard Medical School. Dr Julie is certified in neurodevelopmental treatment (pediatrics) NDTA which has its foundation from the early works of Dr Bobath. Recent awards include the outstanding award for Speech Language Pathologist in Hialeah, Fl for 2018 and the Hall of Fame award for 2019 in Hialeah, Fl. Dr Julie lectured for Advance Magazine for nearly three consecutive years throughout Florida on various topics inclusive of “Chronic Neurological Impairments.” She currently resides in Vero Beach, Fl where she is in private practice.
Abstract:
Statement of the Problem: Many speech-language pathologists are not aware of the underlying causation and treatment strategies of pediatric communication disorders pertaining to the area of neuroscience. Understanding the basics of neurogenesis and neuroplasticity add an essential component necessary for treatment efficacy in the field of speech-language pathology. In addition, understanding the principals of executive functioning play a key role regarding the attentional network of all individuals, especially with patients presenting with a diagnosis of attention deficit disorder, inclusive of those with a high impulsivity index. Sensory modulation also plays a key role in the habilitation or rehabilitation of adapting to the environment in an effective manner necessary for activities of daily living. Attention to task and effective orientation to one’s environment are highly dependent upon the patients’ self-regulation and sensory processing. The focus of this presentation is in the field of pediatrics; however, it is important to understand that neuroplasticity continues throughout adulthood. Modulation of mood, as well as creating new pathways for learning and memory are examples of where neurogenesis and neuroplasticity are salient features in the areas of pediatrics and geriatrics. Another area that negatively impacts learning in people of all ages is the detrimental impact of inflammation and its relation to the immune system. This is understanding the impact of outcome measures during the waxing and waning of the patients’ immune system. In conclusion, it is vital that speech-language pathologists do not solely rely on standardized testing as the determination of eligibility and discharge services, yet add to the evaluation and treatment process the impact of the basics of neuroscience.
Zohidjon Nurmanovich Ismailov
Republic Children’s Rehabilitation Centre, Uzbekistan
Title: Improvement of Rehabilitation Activities in Treatment of Post-Injection Mono-Neuropathies in Children
Biography:
Abstract. The aim of our research was to improve rehabilitation measures in children with a disease of the neuro-motor sphere. To conduct research, 100 children aged 3 to 18 years who were in stationary and outpatient areas in the Republican Children's Rehabilitation Center were examined. Tashkent. Rem-Ex created on the Android platform.
Relevance. Among the diseases of the peripheral nervous system in children accompanied by pain syndromes, post injection mononeuropathies of the lower extremities are most prevalent, with trauma of the peripheral nerves in children in second place. The prevalence of diseases of the peripheral nervous system (PNS) in children and adolescents under the age of 14 in Uzbekistan is 140 cases per 100,000 population, the primary incidence is 64 per 100 thousand population
Therefore, the question of modern principles of rehabilitation of children with diseases of the neuromotor sphere is acute, since step-by-step rehabilitation methods have not been developed and this issue is still relevant today.
Objective The aim of our study was to improve rehabilitation measures in children with diseases of the neuromotor system.
Materials and methods. For the study, we examined 100 children aged 3 to 18 years who were inpatient and outpatient treatment at the Republican Children's Rehabilitation Center for Diseases of the Musculoskeletal System of Tashkent. Of the 100 children examined, 80 practically healthy children with various types of neuropathy from the use of NSAIDs (injections), 10 children with neuropathies as a result of prolonged use of orthoses, 10-monoparesis of the lower extremities of various etiologies. Depending on the treatment methods used, all patients were divided into groups (table 1).
Table 1. The division into groups depending on the methods of treatment used (n = 100).
|
Groups |
Quantity and age |
Rehabilitation Methods |
|
Basic |
36 (36%) children 10,05±0,27 |
Traditional treatments |
|
Comparison group |
64 (64%) children, 9,8±0,25 |
Developed rehabilitation methods |
The comparison group used the mobile application (Rem-Ex) developed by us.
Results. The developed software (Rem-Ex) was created on the platform and includes visualization, assessment and step-by-step comprehensive rehabilitation depending on the age of the child and individual gender differences. According to a neurological examination, statistically significant results were obtained: in 57.3 ± 4.0% of children, tremor of the lower extremities was stopped (p≤0.05); the number of children with no restrictions on manual functions in the main group was 61.6 ± 5.8% compared with the control group (21.8 ± 3.4%, p≤0.05). The severity of muscle hypotrophy (feet, legs) decreased in 68.5 ± 7.2% in the main group, compared with the control (24.3 ± 3.8%, p≤0.05). The function of movement without assistive devices improved in 73.2 ± 8.6% in the main group versus 42.3 ± 4.4% (p≤0.05) in the control group. The frequency of gross movement disorders decreased from 67.3 ± 4.5% to 13.8 ± 2.4% (p≤0.05) in the main group versus 44.6 ± 3.7% in the control group (p≤0, 05). The ability to stand (walk) on toes was normalized in 65.7 ± 7.6% of children (p≤0.05) compared with the control group (34.4 ± 4.7%, p≤0.05). The ability to walk on the heels improved in 55.2 ± 6.4% in the main group versus 29.6 ± 4.7%, p≤0.05 in the control group. The severity of steppage decreased from 45.8 ± 4.9% to 10.3 ± 2.4% in the main group versus 21.6 ± 4.3% in the control group (p≤0.05).
Abstract:
Zohidjon Nurmanovich Ismailov is working as pediatric neurologist and Chairman of the Commission for information Communication Technology at Republic Children’s Rehabilitation Canter with diseases of bearing –movable system and pediatric neurologist in the ООО « International Trade and Production» CITY MED clinic
Veronika E. Neubrand
University of Granada, Spain
Title: The atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia
Biography:
Veronika Neubrand possesses a Biology degree from the University of Heidelberg and a PhD from the European Molecular Biology Laboratory (EMBL) and the University of Heidelberg, Germany. Currently she holds an associate professorship at the department of Cell Biology at the University of Granada, Spain.
In 2009 at the IPBLN-CSIC, Granada, Spain, she started to study the cell biology of microglia, the immune cells of the brain, which play an essential role in neuroinflammation, an important hallmark of neurodegenerative diseases, such as Alzheimer´s and Parkinson´s. In 2014, she was awarded a research grant by the Michael J Fox Foundation, USA. As principle investigator of this grant she identified molecules involved in the generation of CNS-supporting microglia, which represent drug targets for the diseases mentioned above. From 2005 to 2009, Veronika investigated the molecular mechanisms of axonal and dendritic growth in neurons at the Cancer Research UK London Research Institute.
Abstract:
Over-activated microglia, the resident immune cells of the brain, play a central role during neuroinflammation, leading to neuronal cell death and neurodegeneration, for example in Alzheimer´s and Parkinson´s disease. Reversion of these over-activated microglia to a neuroprotective phenotype could regenerate a healthy Central Nervous System (CNS)-supporting microglial environment. Our aim was to identify a dataset of intracellular molecules in primary microglia that play a role in the transition of a neurotoxic phenotype to a ramified, neuroprotective one. To do this, we exploited the anti-inflammatory and neuroprotective properties of conditioned medium of adipose-derived mesenchymal stem cells (CM) as a tool to generate the neuroprotective phenotype of microglia in vitro, and we set up a microscopy-based siRNA screen to identify its hits by cell morphology.
We assayed an siRNA array targeting more than 150 genes that codify proteins of cytoskeleton and inflammatory pathways in microglia. From them, siRNA-downregulation of more than 40 genes significantly inhibited the CM-induced transition from a neurotoxic to a neuroprotective microglia phenotype, and 50 siRNA-downregulated genes had the opposite effect. As a proof-of-concept, seven of these targets were validated by downregulation of protein expression with individual siRNAs. They were assayed in functional screens that revealed that the atypical RhoGTPase RhoE/Rnd3 is necessary for BDNF expression and plays an essential role in controlling microglial migration.
Besides the identification of RhoE/Rnd3 as a novel inducer of a neuroprotective phenotype in microglia, we propose a list of potential targets to be further confirmed with selective activators or inhibitors.
Acknowledgements: This work was supported by a Michael J Fox Foundation research grant.
Biography:
She is an associate research scientist at Afchempharm, working on a multidisciplinary PhD project with the company and department of neuroscience (SITraN) at The Sheffield University. She currently completing the final year of my PhD. The focus of her thesis is using computational docking screening and synthetic procedures to design and develop a novel antagonist for N-methyl-D-aspartate receptors (NMDAR). These receptors have been known to contribute in excitotoxicity that leads to neurodegeneration and death of brain cells. Throughout her career she hoping to provide more insight on these complex biological systems. Ultimately, hoping to contribute to developing potential therapeutics for these detrimental diseases.
Abstract:
Acute ischaemic stroke (AIS) is a global burden. In the UK, stroke is still one of the leading causes of death and nearly 2/3 of stroke survivors leave hospital with a disability. Effective neuroprotective drugs can meet the significant need for AIS management by protecting patients prior to a stroke insult, and aiding them in recovery. Excitatory neurotransmission conducted by the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor is essential for the development and function of the central nervous system (CNS). However, excessive stimulation of these membrane receptors has been implicated as one of the key contributors of neural injury in AIS and several other neurodegenerative diseases. Our aims are to use rational drug design and structure based virtual screening methods to design small molecule inhibitors which will target a short peptide sequence of the ligand binding domain of the NMDA receptor. This novel site was identified to bind to antibodies and protect against ischeamic stroke in rodent models. Using in silico methods we have identified compounds that interact well with the peptide sequence. Several compounds were tested for their efficacy and safety profiles in in vitro assay that induces NMDAR excitotoxicity such as LDH cytotoxicity assay using primary cortical neurons from mice. In addition, we also used the high content imaging analysis system (Columbus) to assess nuclear morphology of the cells when exposed to different concentrations of compounds in presence of the toxin. We have completed the virtual screening segment of the project, screening over ~25,000 compounds from commercial vendors and in-house libraries. We have narrowed these down to 27 compounds that interact well with the novel site of NMDAR, and tested them in our in vitro model. Three of these compounds were shown to be neuroprotective with reduction of cell death up to 10% at 1 and 10μM concentrations. These properties are useful to characterise further in the binding assay as well as in in vivo experiments to further understand the mode of action of the compounds.
Hsinsung Yuan
Nanjing Meishan Hospital, China
Title: Early symptom non-improvement and aggravation are associated with the treatment response to SSRIs in MDD: a real world study
Biography:
Hsinsung Yuan has her expertise in improving early treatment effect in major depressive disorder and anxiety-related disorder through facilitating elaborate measurement and datafication of the treatment-related symptoms changes. She has devoted in modelling symptoms connection patterns which flowing on the basis of the development of personality and its interaction with complex real world information in order to individually moderate treatment in early treatment stage to improve well-being and satisfaction in patients
Abstract:
Purpose: Early improvement has been proved to be able to predict the long-term treatment response. However, there is still no efficient strategy for switching medications when a patient failed to reach early improvement at the second week. This study focused on the predictive value of treatment-related symptom aggravation, which is a mixture of side effects, nocebo effects and disorder itself, in each item of the HAMD scale for the treatment response to SSRI monotherapy to provide a reference for switching antidepressants to enhance early treatment efficacy.
Patients and methods: Our study was an observational real-world study that enrolled 90 first-onset untreated outpatients in the outpatient department of Huashan Hospital. Patients who did not achieve the threshold of early improvement in the second week after starting treatment were switched to another SSRI monotherapy. The patient was followed up at 2, 4, 8 and 12 weeks after initiation of treatment. We analysed the relationship between the data with the change in each symptom on the HAMD-17 scale and the treatment efficacy.
Results: Early improvement predicted the treatment response at the end of 12 weeks (χ2=19.249, p<0.001), whereas early non-improvement in difficulty with falling asleep (OR=9.487, 95% CI: 1.312-68.588) and mood anxiety (OR=12.947, 95% CI: 1.99-82.246) were associated with a poor response. At Week 2, general somatic symptom aggravation was associated with a poorer response (OR=73.337, 95% CI: 2.232->>1); treatment-emergent headache (t=-9.521, p<0.001) and tremor (t=3.660, p=0.001) were associated with treatment efficacy. In addition, the increase in suicidal thoughts once treatment began had no relationship with the treatment response (OR=0.821, P=0.872).
Conclusion: This study suggests that patients with early non-improvement in falling asleep and anxiety are not suitable for switching SSRI monotherapy. Patients with treatment-emergent symptoms, especially headaches and tremors, are not suitable for switching monotherapy to another SSRI.
Biography:
My first approach to the area of neuroscience began in 2014 when I entered the Laboratory of Molecular and Clinical Pharmacology of the Faculty of Medicine of the University of Chile, evaluating the brain changes that occur after perinatal asphyxia, an alteration right before, during or just after delivery, which leads to the deprivation of the bioavailability of oxygen in the newborn. Previously I had worked in a genetics and genomics laboratory of the same University, which along my undergraduate profession of Medical Technologist with specialty in Morphophysiopathology and Cytodiagnosis, encouraged me to start a research focused on the genetic and genomic analysis of the brain after hypoxia. In addition to the research area, I work in the area of university management and teaching at the Universidad del Desarrollo, Santiago of Chile, and also as scientific advisor in a genetic diagnostic laboratory called Bioscan.
Abstract:
Perinatal asphyxia (PA) is characterized by interruption of oxygen bioavailability at birth. Hypoxia implies HIF-1α activation, a key sentinel protein, which, upon translocation to the nucleus, binds to response elements (HREs), promoting the transcription of several genes. Potential genes activated by HIF-1α under hypoxic conditions were identified in the rat genome by extracting promoter sequences of Rattus Norvegicus from the UCSC database Genome Browser, using the latest version of rat genome. A promoter sequence of 39595 transcripts was first obtained, identifying then 8762 genes with the HIF-1α binding sequence (5`-RCGTG-3`) with the “R” software. 8762 genes were introduced to the Gene Ontology platform for performing an enrichment analysis, selecting the following processes linked to PA: Hypoxia (865 genes); Glucose metabolism (330 genes); Neurogenesis (1243 genes); Apoptosis (814 genes); Hematopoiesis (165 genes), and Regulation of gene expression (2076 genes). The 865 hypoxia associated genes were further selected and compared with experimental data by ChIP-Seq, with 772 and 98 genes, from the human and zebrafish genomes, respectively, finding that (i) 72 genes were shared by human and rat; (ii) 10 genes were shared by zebrafish and rat; (iii) 8 genes were shared by human and zebrafish, and (iv) 3 genes were shared by the three species. The 8762 genes were then analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) platform, selecting the HIF-1 pathway, identifying 47 genes. The 79 genes filtered for human, zebrafish and rat, were compared with the 47 genes obtained by the KEGG platform, yielding 12 genes. Finally, 12 genes were compared with 47 genes referred by the literature to be associated to PA, identifying 5 genes: Bcl2, Hif-1α, Ldha; Pdk1, and Vegfa. Analysis of sequence conservation was performed for each species, using the Ensembl Genes database, obtaining an 80% of conservative sequences for all cases.
Nana Tsiklauri
Tbilisi State Medical University, Georgia
Title: The study of antinociceptive tolerance to cannabinoids microinjected into central nucleus of amygdala in rheumatoid arthritis model of rats
Biography:
Abstract:
Introduction. Rheumatoid arthritis (RA) is the chronic (long-term) disease, that cause pain and limited motion and function of many joints. It has been discovered that cannabinoid receptors are expressed in the amygdala, and their activity contributes to the dissociative effect of cannabis on pain perception. It has been also shown In our investigations, that repeated microinjection of NSAIDs into central nucleus of amygdala induces development of tolerance to them. Therefore very interesting to figure out if repeated microinjections of cannabinoids into the central nucleus of amygdale could induce tolerance effects to them. There are many studies examining the effects of cannabinoids in relief of acute and chronic inflammatory pain, and many researches try to prove high efficiency and demonstrate new capabilities of these drugs in rheumatoid arthritis treatment. But much less is known about their side effects like tolerance after repeated administration for long-term treatment. Therefore we studied the antinociception and tolerance during chronic pain in rheumatoid arthritis induced by administration of delta-9- tetrahydrocannabinol (Δ9-THC) into the central nucleus of amigdala for five consecutive days.
Methods. We Induced rheumatoid arthritis in rats by immunization, with an emulsion of complete Freund,s adjuvant and type II collagen (CII), into the tail and monitored of arthritis incidence during 5-8 weeks. : After developing arthritis incidence, surgical procedures for streotaxically bilaterally inplant cannulas into central nucleus of amygdala(CeA) . Repeated microinjections by Δ9â€THC During five consecutive days, one times in day and then testing antinociception using the tail-flick (TF) reflex and on the latency of thermal paw withdrawal reflex and mechanical threshold of paw withdrawal.
Results. Microinjection of Δ9â€THC into the central nucleus of amygdala produced antinociception, as detected by increased latencies in the TF and thermal paw and mechanical paw withdrawal threshold tests as compared to the baseline and to the control group that received saline microinjections in CeA.
On subsequent days Δ9â€THC microinjections caused progressively less antinociception i.e., (tolerance), so that by day 5 there was no effect (i.e., injected groups on day 5 were not significantly different from saline microinjections in all tests).
Conclusions. Here we demonstrated that microinjection of Δ9â€THC, injected into the central nucleus of amygdala, induced antinociception in rheumatoid arthritis model of rats and repeated administration of cannabis induced development of tolerance to them.
In this work we have shown that a long-term use of cannabinoids cause development of tolerance toward them, so this is one of the side effects of cannabinoids, and using for treatment these drugs in rheumatoid arthritis is limited.
Acknowlegement. This research was supported by the grant from Shota Rustaveli National Science Foundation of Georgia (YS17-53).
Rose- Marie Boylan
Registered Dietitian, Life Coach Salutogenesis/Lifestyle medicine, Canada
Title: Female psyche, sexual repression & mind-body health
Biography:
Rose-Marie Boylan, BSc. M.A. is a Dietitian by trade. She has worked across 6 of the largest pharmaceutical companies and 4 smaller organizations for over 27 years up to executive levels. She has specialized in patient access to medicines, patient reported outcomes, health economics, policy influence for patient self-sovereignty. In parallel, Rose-Marie has researched for over 13 years social, civil and political cost-consequence & cost-benefits of psychiatry, transpersonal psychology & human flourishing in violence survivors. This includes a cost-consequence model. She completed her Masters in 2009 in Leadership Studies with research on the optimum levels that humans can attain in a life time for developing the highest levels of moral, emotional & cognitive intelligence through self-actualization & post-traumatic growth. Leveraging the research of Abraham Maslow & Jane Loevinger on ego development she developed a model which defines mind health vs. psychopathologies. Additionally, for 13 years Rose-Marie studied mind-body medicine with the likes of Dr. Herbert Benson from Harvard’s Mind Body Institute, Jon Kabat- Zin, Saki Santorelli from the University of Massachusetts School of Preventive & Behavioral Medicine. She has researched and tested all forms of meditation, therapeutic & mindfulness yoga in teacher trainings which she has taught to trauma survivors & professionals in crisis.
Abstract:
The clitoris is likely the most pivotal organ in female sexual health. The clitoris is considered the female version of the penis. Conclusions of the 'Comprehensive Review of the Clitoris and its roles in Female. Sexual Function, 2015; D. Mazloomdoost states that the clitoris should be allocated the appreciation it deserves, it is worthy of examining as a unique entity". In mental health & neuroethics a female’s body-mind awareness of this organ should be investigated further. Specifically, how sexual repression of this highly developed neurological system works and its underlying impact on mind-body health, depression, anxiety, addiction disorders and other physiological diseases. Specifically analyzing the deleterious effects of external dopamine arousal addictions and how understanding female psyche as it relates to mind-body pleasure can alter patient health outcomes. According to Abraham Maslow, 99% of humans can develop psychopathologies when there is basic need eprivation. Rarely, however in mental health & medicine is there a medical inquiry around basic need deprivation. Lower order needs for food, shelter, safety and sex may be an underlying cause of psychopathologies. Addressing basic need deprivation or higher order need deprivation should be considered first-line. The use of medications to highly sensitive persons which alter personal authenticity, the mind, inherent belief systems and paralyze the neurological pathways derived from the clitoris should be evaluated based on adverse events and lifestyle implications. Specifically, as it relates to quality of life measures for single females, couples and male basic needs. The notion of psychoanalytical theory (identifying pathogenesis before suggesting salutogenic alternatives) requires a rethinking of current diagnostic criteria based on an investigative inquiry into basic need & higher order need deprivation. Human basic need deprivation has a paramount role in driving underlying pathologies & predisposing the organism to disease and other chronic illnesses.
Sexual health, consciousness and female evolution to the highest levels of ego development & brain development are paradoxically linked. The clitoris like the pineal gland could be a gateway for females in reaching the highest levels of cognitive, emotional, moral intelligence. Body-mind awareness can move the subject from perhaps the lowest levels of ego-development following trauma to the highest levels for human leadership & moral, cognitive & emotional intelligence. The researcher discusses the concept of ego-development according to Jane Loevinger’s model and Abraham Maslow’s research on self-actualization & self-transcendence. The notion of female sexuality, intelligence & spirituality is discussed under the optic of current medical practices, neurology and psychiatry and their impact on female human potential.
The clitoris combined with mind-body awareness techniques may be a pivotal catalyst for orgasmic functioning, neurological, immunological strength, happiness & mental health in females.
Julio López Argüelles
Gustavo AldereguÃa Hospital, Cuba
Title: Factors related with frontal dysfunction in early stages of Parkinson Disease
Biography:
Julio López Argüelles specialist in neurology at Gustavo Aldereguía Hospital in Cienfuegos City. Master in medical emergencies. Assistant professor. Assistant Investigator. Specialist research in Parkinson's disease and dementia, with multiple publications on the subject. Editor and reviewer of multiple journals.
Abstract:
Introduction: Parkinson Disease (PD) although described initially by James Parkinson as a disease with motor disorder it has been demonstrated that the cognitive disorders in the form of disejecutive syndrome are frequent worsening with the evolution. Objective: To characterize the frontal dysfunction (FD) in the patients with PD and to determine the factors related with frontal dysfunction in early stages. Method: We studied 125 patients with diagnosis of idiopathic PD and Hohen and Yahr Stages <2, to those which it was carried to them out survey with demographic, clinical and neuropsychological data studies included the Frontal Assesment Batery (FAB). Results: The mean age was of 68.1 ± 8.6, the onset age was of 62.6 ± 10.5, the diestrums predominated and those which initiated with tremor. Of the 125 patients 71.4% presented FD, with an average of the FAB of 11.82 ± 3.7. The age (R=-0,45; p<0,001) and onset age (R=-0,33; p=0,02) showed inversely proportional correlation with the FD. Other related variables were the schooling up to second level (p=0,003) and the rural origin with significance <0,001. Conclusions: The age and onset age higher than 60 years, the lower schooling than second level of teaching, rural origin and the presence of cognitive dysfunction are related to FD in early stages of PD.
Bakr Abo Jarad
Sheffa hospital, Palestine
Title: Acute spinal compression caused by spinal aggressive hemangioma
Biography:
Abstract:
Vertebral hemangioma is a one of common benign lesion of the spine that rarely comes with the symptom, but sometimes can be associated with bone expansion and cord compression so need urgent management; management lines include arterial embolization, decompression surgery then radiation.
Aggressive vertebral hemangioma can be categorized into 4 groups, 1st group show mild bony destruction without symptom and observation is recommended here; type 2, active bony destruction with pain only and it can be treated by radiotherapy or alcohol injection; type 3, aggressive asymptomatic lesion with epidural or soft tissue extension and may be treated by observation; type 4, aggressive neurological deficit with epidural extension and need treatment by surgery or other choices of treatment
We present a case of 22-year-old male presented with severe back pain with progressive lower limb weakness and decreased sensation in both lower limbs, MRI Show infiltration mass of T8 vertebra that expanded to compress spinal cord, all imaging modalities that utilized to diagnosis suggest aggressive hemangioma, laminectomy decompression was done and final pathological report confirmed aggressive hemangioma, patient symptom relieved with full muscle power
Liliya Abramova
FSBSI MHRC, Russia
Title: Agomelatine as ameans of effective therapy of anhedonic endogenous depressions
Biography:
Abstract:
Background: Anhedonia determines the specificity of the clinical picture and the severity of state in the structure of endogenous depressions. The aim of the study was to investigate the therapeutic picture of new generation antidepressant with melatoninergetic effect of agomelatine (valdoxane) in anhedonic depressions and to develop personified indications for its use. Material and methods: The study was carried out as an open label prospective with informed consent of patients for participation in it. A total of 30 patients with endogenous depressions. were examined, the clinical picture of which was determined by anhedonic disorders in various spheres of psychic activity; in the sphere of interests, social activity, emotional involvement, eating/drinking (F31.3-4; F32.1-2, and F33.1-2 according to ICD-10). All the patients received course treatment (30 days) with agomelatine (AG) at a daily dose of 25-50 mg. Clinical-psychological, psychometric (HAMD, SHAPS rating scales), and statistical methods were used. AG therapeutic effect was evaluated according to Mean total score (MTS) reduction of the examined parameters. Results: Total AG antidepressive effect made up 78,9% of MTS reduction according to HAMD. Differences in therapeutic AG effect were revealed both with respect to anhedonic component of depression in whole, as well as in the dynamics of its indices according to separate SHAPS spheres. By the end of the study the index in the sphere of interests was high in percent age terms, buti was inferior to in dices of reduction in anhedonia in other spheres: social activity, emotional involvement, making up 88.2% against 91.7; 95.2% correspondingly. Conclusion: The results of the conducted study allow considering the method of AG course treatment as preferable and highly effective in anhedonic endogenous depressions. High therapeutic antianhedonic AG efficacy, rapidity of detection of therapeutic impact in combination with good drug tolerability substantiated the choice of the given method of anhedonic depressions treatment.
Mishaal Alkhaldi
King Fahad Specialist Hospital Dammam, Saudi Arabia
Title: Does Spinal Ischemia reperfusion injury respond to Rehabilitation?
Biography:
Abstract:
Spinal ischemia-reperfusion injury (IRI) is one of the worrisome issues to the neurosurgeons, as it plays a big role in increasing length of stay and cost of hospitalization. Unfortunately, all the investigations attempted to control the IRI found no clear solution. This is possibly due to many factors such as the presence of a large number of the experimental protocols. In addition, the complete understanding of the IRI mechanism is not fully understood yet.
One of the possible complications for the spinal IRI is paraplegia. Incomplete paraplegia has been proven to be effectively treated by neuro-rehabilitation programs .However, no study was found in the literature investigating the effectiveness of the neuro-rehabilitation therapy for this injury.
In this case report we discuss a case with spinal IRI led to paraplegia leaving the patient bed bound.This patient underwent an intensive rehabilitation in a dedicated unit. Fortunately, patient was discharged fully independent and ambulatory.
Mustapha Peter Tarfa
Gombe State University, Nigeria
Title: The Role of Programmed Cell Death 'Apoptosis' in the Development of Inner Sulcus in the Cochlea
Biography:
Tarfa M. Peter has completed his M.Sc. from University of Maiduguri, Borno State, Nigeria. He is the Histology lecturer, in the Department Human Anatomy, Gombe State University. He has published more than 10 papers in reputed journals and is presently undergoing his Ph. D in Ahmadu Bello University Zaria.
Abstract:
Hearing loss is one of the most common chronic diseases that affect both young and old but it is most prevalent in old people. This condition is generally irreversible in humans and can be due to the loss of hair cells, which are unable to regenerate. However, recent evidence of some regenerative ability reported in a number of non-mammal vertebrates have given us hope that, in the future a solution may be discovered. Although several advances have been recorded in this field in recent times and ere are still challenges ahead. This study tried to investigate he formation of the inner sulcus located in the cochlea, as it is thought that, the processes involved during the development of this important region are most likely due to apoptosis or another type of programmed cell death, although this has not yet been confirmed.
Mouse expressing an EGFP (green fluorescent protein) reporter at the Tecta locus was used. Specimens were stained with phalloidin as a general cell stain of f-actin and this was combined with (Terminal deoxynucleotidyl transferase dUTP Nick End) TUNEL staining in order to observe whether dying cells are the result of programmed cell death.
Very little TUNEL staining was observed in the developing sulcal region, although some were seen in the associated mesenchymal cells in the cochlea. In some of the sections, Blebbing as well as extrusion of some cells that are thought to be undergoing programmed cell death were evident during the formation of the sulcus. The formation of the sulcus occurs earlier in the basal region of the cochlea than in the apical part following the regression of the greater epithelial ridge (GER) cells. Counting of nuclei in the sulcal region during the formation suggest that cells are being lost. It is not easy to establish whether these cells that are being removed could be due to apoptosis or another type of programmed cell death.
Biography:
Dr. Sullivan is an Assistant Professor at Touro College Physician Program in New York. He received a Medical degree with a focus in neurology and a Doctor of Philosophy degree for work in neurophysiology at New York Medical College. He is currently teaching medical, PT and PA students in neurology, cardiology and physiology. His research interests include treatments for chronic trauamatic encephalopathy, patient compliance, and metal dysregulation
Abstract:
The role of zinc (Zn2+), a modulator of N-methyl-D-aspartate (NMDA) receptors, in regulating long-term synaptic plasticity at hippocampal CA1 synapses is poorly understood. The effects of exogenous application of Zn2+ and of chelation of endogenous Zn2+ were examined on long-term potentiation (LTP) of stimulus-evoked synaptic transmission at Schaffer collateral (SCH) synapses in field CA1 of mouse hippocampal slices using whole-cell patch clamp and field recordings. Low micromolar concentrations of exogenous Zn2+ enhanced the induction of LTP, and this effect required activation of NMDA receptors containing NR2B subunits. Zn2+ elicited a selective increase in NMDA/NR2B fEPSPs, and removal of endogenous Zn2+ with high-affinity Zn2+ chelators robustly reduced the magnitude of stimulusevoked LTP. Taken together, our data show that Zn2+ at physiological concentrations enhances activation of NMDA receptors containing NR2B subunits, and that this effect enhances the magnitude of LTP.
Jose Maria G. Pelayo III
Music Psychology Center, Philippines
Title: Music therapy for children with autism spectrum disorder
Biography:
Prof. Jose Maria G. Pelayo III is an author and psychology researcher who has published articles in several international journals and has presented academic papers in international conferences. He has been an author/professor/researcher in psychology for 18 years. He has published textbooks in Psychology and Criminology. His research studies include psychology, music psychology, criminology, social psychology, social development and psychoanalysis. He is the founder of the first Music Psychology Center (MPC) in the Philippines, located in Angeles City, Pampanga
Abstract:
The aim of the researchers was to determine if there are alternative methods in treating children with autism. Children diagnosed with autism are currently under special schools with a different type of curriculum. Many methods have been used by psychologists and psychiatrists to treat children diagnosed with autism. Children with mental or physical disabilities have been isolated in the common educational environment. The focus of this study was to try to help and enhance methods that may, in return, aide in the rehabilitation and treatment of children with mental and physical disabilities, specifically children with autism