Search results for: neuro-vascular deficits
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 263

Search results for: neuro-vascular deficits

203 Pomegranates Attenuates Cognitive and Behavioural Deficts and reduces inflammation in a Transgenic Mice Model of Alzheimer's Disease

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

Abstract:

Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

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202 Date Palm Fruits from Oman Attenuates Cognitive and Behavioral Defects and Reduces Inflammation in a Transgenic Mice Model of Alzheimer's Disease

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

Abstract:

Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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201 Challenging Weak Central Coherence: An Exploration of Neurological Evidence from Visual Processing and Linguistic Studies in Autism Spectrum Disorder

Authors: Jessica Scher Lisa, Eric Shyman

Abstract:

Autism spectrum disorder (ASD) is a neuro-developmental disorder that is characterized by persistent deficits in social communication and social interaction (i.e. deficits in social-emotional reciprocity, nonverbal communicative behaviors, and establishing/maintaining social relationships), as well as by the presence of repetitive behaviors and perseverative areas of interest (i.e. stereotyped or receptive motor movements, use of objects, or speech, rigidity, restricted interests, and hypo or hyperactivity to sensory input or unusual interest in sensory aspects of the environment). Additionally, diagnoses of ASD require the presentation of symptoms in the early developmental period, marked impairments in adaptive functioning, and a lack of explanation by general intellectual impairment or global developmental delay (although these conditions may be co-occurring). Over the past several decades, many theories have been developed in an effort to explain the root cause of ASD in terms of atypical central cognitive processes. The field of neuroscience is increasingly finding structural and functional differences between autistic and neurotypical individuals using neuro-imaging technology. One main area this research has focused upon is in visuospatial processing, with specific attention to the notion of ‘weak central coherence’ (WCC). This paper offers an analysis of findings from selected studies in order to explore research that challenges the ‘deficit’ characterization of a weak central coherence theory as opposed to a ‘superiority’ characterization of strong local coherence. The weak central coherence theory has long been both supported and refuted in the ASD literature and has most recently been increasingly challenged by advances in neuroscience. The selected studies lend evidence to the notion of amplified localized perception rather than deficient global perception. In other words, WCC may represent superiority in ‘local processing’ rather than a deficit in global processing. Additionally, the right hemisphere and the specific area of the extrastriate appear to be key in both the visual and lexicosemantic process. Overactivity in the striate region seems to suggest inaccuracy in semantic language, which lends itself to support for the link between the striate region and the atypical organization of the lexicosemantic system in ASD.

Keywords: autism spectrum disorder, neurology, visual processing, weak coherence

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200 Neuromyelitis Optica area Postrema Syndrome(NMOSD-APS) in a Fifteen-year-old Girl: A Case Report

Authors: Merilin Ivanova Ivanova, Kalin Dimitrov Atanasov, Stefan Petrov Enchev

Abstract:

Backgroud: Neuromyelitis optica spectrum disorder, also known as Devic’s disease, is a relapsing demyelinating autoimmune inflammatory disorder of the central nervous system associated with anti-aquaporin 4 (AQP4) antibodies that can manifest with devastating secondary neurological deficits. Most commonly affected are the optic nerves and the spinal cord-clinically this is often presented with optic neuritis (loss of vision), transverse myelitis(weakness or paralysis of extremities),lack of bladder and bowel control, numbness. APS is a core clinical entity of NMOSD and adds to the clinical representation the following symptoms: intractable nausea, vomiting and hiccup, it usually occurs isolated at onset, and can lead to a significant delay in the diagnosis. The condition may have features similar to multiple sclerosis (MS) but the episodes are worse in NMO and it is treated differently. It could be relapsing or monophasic. Possible complications are visual field defects and motor impairment, with potential blindness and irreversible motor deficits. In severe cases, myogenic respiratory failure ensues. The incidence of reported cases is approximately 0.3–4.4 per 100,000. Paediatric cases of NMOSD are rare but have been reported occasionally, comprising less than 5% of the reported cases. Objective: The case serves to show the difficulty when it comes to the diagnostic processes regarding a rare autoimmune disease with non- specific symptoms, taking large interval of rimes to reveal as complete clinical manifestation of the aforementioned syndrome, as well as the necessity of multidisciplinary approach in the setting of а general paediatric department in аn emergency hospital. Methods: itpatient's history, clinical presentation, and information from the used diagnostic tools(MRI with contrast of the central nervous system) lead us to the conclusion .This was later on confirmed by the positive results from the anti-aquaporin 4 (AQP4) antibody serology test. Conclusion: APS is a common symptom of NMOSD and is considered a challenge in a differential-diagnostic plan. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing thorough physical examinations are essential if we are to reduce and avoid misdiagnosis.

Keywords: neuromyelitis, devic's disease, hiccup, autoimmune, MRI

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199 The Organizational Structure of the Special Purpose Vehicle in Public-Private Partnership Projects

Authors: Samuel Capintero

Abstract:

Public-private partnerships (PPP) arrangements have emerged all around the world as a response to infrastructure deficits and the need to refurbish existing infrastructure. During the last decade, the Spanish companies have dominated the international market of PPP projects in Latin America, Western Europe and North America, particularly in the transportation sector. Arguably, one of the most influential factors has been the organizational structure of the concessionaire implemented by the Spanish consortiums. The model followed by most Spanish groups has been a bundled model, where the concessionaire integrates the functions of concessionaire, construction and operator companies. This paper examines this model and explores how it has provided the Spanish companies with a comparative advantage in the international PPP market.

Keywords: PPP, project management, concessionaire, concession, infrastructure, construction

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198 Analysis of Gait Characteristics Using Dynamic Foot Scanner in Type 2 Diabetes Mellitus

Authors: C. G. Shashi Kumar, G. Arun Maiya, H. Manjunath Hande, K. V. Rajagopal

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Background: Diabetes mellitus (DM) is a metabolic disorder with involvement of neurovascular and muscular system. Studies have documented that the gait parameter is altered in type 2 diabetes mellitus with peripheral neuropathy. However, there is a dearth of literature regarding the gait characteristics in type 2 diabetes mellitus (T2DM) without peripheral neuropathy. Therefore, the present study is focused on identifying gait changes in early type 2 diabetes mellitus without peripheral neuropathy. Objective: To analyze the gait characteristics in Type 2 diabetes mellitus without peripheral neuropathy. Methods: After obtaining ethical clearance from Institutional Ethical Committee (IEC), 36 T2DM without peripheral neuropathy and 32 matched healthy subjects were recruited. Gait characteristics (step duration, gait cycle length, gait cycle duration, stride duration, step length, double stance duration) of all the subjects were analyzed using Windtrack dynamic foot scanner. Data were analyzed using Independent‘t’ test to find the difference between the groups (step duration, gait cycle length, gait cycle duration) and Mann-Whitney test was used to analyze the step length and double stance duration to find difference between the groups. Level of significance was kept at P<0.05. Results: Result analysis showed significant decrease in step duration, gait cycle length, gait cycle duration, step length, double stance duration in T2DM subjects as compared to healthy subjects. We also observed a mean increase in stride duration in T2DM subjects compared to healthy subjects.

Keywords: type 2 diabetes mellitus, dynamic foot scan, gait characteristics, medical and health sciences

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197 The Perceived Role of the Cooperating Teacher: Differing Perspectives on Enactment

Authors: Mary Isobelle Mullaney

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The purpose of this research was to explore the attitudes of student Art and Design teachers (n=79) and their cooperating teachers in the Republic of Ireland (n=83) as to their interpretation of the role in teacher education. The role is outlined in terms of how the Teaching Council defines the role and then how the students and teachers see it being fulfilled. While overall teachers rated themselves as fulfilling the role expected of them, the interpretation varied greatly, with considerable deficits reported regarding guidance given in planning, observation of the student teacher, and feedback given. Overall, students saw teachers as fulfilling their role effectively, though there was considerable variation reported in experiences. A focus group was conducted in order to arrive at a more comprehensive understanding of the underlying factors influencing these discrepancies.

Keywords: Irish post primary teaching, cooperating teacher, student teacher, teacher education

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196 The Impact of Trade Liberalization on Current Account Deficit: The Turkish Case

Authors: E. Selçuk, Z. Karaçor, P. Yardımcı

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Trade liberalization and its effects on the economies of developing countries have been investigated by many different studies, and some of them have focused on its impact on the current account balance. Turkey, as being one of the countries, which has liberalized its foreign trade in the 1980s, also needs to be studied in terms of the impact of liberalization on current account deficits. Therefore, the aim of this study is to find out whether trade liberalization has affected Turkey’s trade and current account balances. In order to determine this, yearly data of Turkey from 1980 to 2013 is used. As liberalization dummy, the year 1989, which was set for Turkey, is selected. Structural break test and model estimation results show that trade liberalization has a negative impact on trade balance but do not have a significant impact on the current account balance.

Keywords: budget deficit, liberalization, Turkish economy, current account

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195 Deficits and Solutions in the Development of Modular Factory Systems

Authors: Achim Kampker, Peter Burggräf, Moritz Krunke, Hanno Voet

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As a reaction to current challenges in factory planning, many companies think about introducing factory standards to lower planning times and decrease planning costs. If these factory standards are set-up with a high level of modularity, they are defined as modular factory systems. This paper deals with the main current problems in the application of modular factory systems in practice and presents a solution approach with its basic models. The methodology is based on methods from factory planning but also uses the tools of other disciplines like product development or technology management to deal with the high complexity, which the development of modular factory systems implies. The four basic models that such a methodology has to contain are introduced and pointed out.

Keywords: factory planning, modular factory systems, factory standards, cost-benefit analysis

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194 A Congenital Case of Dandy-Walker Malformation

Authors: Neerja Meena, Paresh Sukhani

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Dandy walker malformation is a generalised disorder of mesenchymal development that affect both the cerebellum and overlying meninges. Classically dandy-walker malformation consists of a triad of- 1:vermian and hemispheric cerebellar hypoplasia 2:cystic dilatation of 4th ventricle 3: enlarged posterior fossa with the upward migration of tentorium(lambdoid- torcular inversion). Clinical presentation: four months old female child with hydrocephalus and neurological symptoms. Generally- early death is common in classic dandy walker malformation. However, if it is relatively mild and uncomplicated by other CNS anomalies, intelligence can be normal and neurologic deficits minimal. Usually, VP shunting is the treatment of choice for this hydrocephalus. Conclusion: MRI is the modality of choice to diagnose posterior fossa malformation. However, it can be ruled out through using during the antenatal check as the prognosis of this malformation is not good; it's better to diagnose it inutero.

Keywords: Dandy Walker, Mri, Earlydaignosis, Treatment

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193 Rehabilitation Team after Brain Damages as Complex System Integrating Consciousness

Authors: Olga Maksakova

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A work with unconscious patients after acute brain damages besides special knowledge and practical skills of all the participants requires a very specific organization. A lot of said about team approach in neurorehabilitation, usually as for outpatient mode. Rehabilitologists deal with fixed patient problems or deficits (motion, speech, cognitive or emotional disorder). Team-building means superficial paradigm of management psychology. Linear mode of teamwork fits casual relationships there. Cases with deep altered states of consciousness (vegetative states, coma, and confusion) require non-linear mode of teamwork: recovery of consciousness might not be the goal due to phenomenon uncertainty. Rehabilitation team as Semi-open Complex System includes the patient as a part. Patient's response pattern becomes formed not only with brain deficits but questions-stimuli, context, and inquiring person. Teamwork is sourcing of phenomenology knowledge of patient's processes as Third-person approach is replaced with Second- and after First-person approaches. Here is a chance for real-time change. Patient’s contacts with his own body and outward things create a basement for restoration of consciousness. The most important condition is systematic feedbacks to any minimal movement or vegetative signal of the patient. Up to now, recovery work with the most severe contingent is carried out in the mode of passive physical interventions, while an effective rehabilitation team should include specially trained psychologists and psychotherapists. It is they who are able to create a network of feedbacks with the patient and inter-professional ones building up the team. Characteristics of ‘Team-Patient’ system (TPS) are energy, entropy, and complexity. Impairment of consciousness as the absence of linear contact appears together with a loss of essential functions (low energy), vegetative-visceral fits (excessive energy and low order), motor agitation (excessive energy and excessive order), etc. Techniques of teamwork are different in these cases for resulting optimization of the system condition. Directed regulation of the system complexity is one of the recovery tools. Different signs of awareness appear as a result of system self-organization. Joint meetings are an important part of teamwork. Regular or event-related discussions form the language of inter-professional communication, as well as the patient's shared mental model. Analysis of complex communication process in TPS may be useful for creation of the general theory of consciousness.

Keywords: rehabilitation team, urgent rehabilitation, severe brain damage, consciousness disorders, complex system theory

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192 Effects of Oxytocin on Neural Response to Facial Emotion Recognition in Schizophrenia

Authors: Avyarthana Dey, Naren P. Rao, Arpitha Jacob, Chaitra V. Hiremath, Shivarama Varambally, Ganesan Venkatasubramanian, Rose Dawn Bharath, Bangalore N. Gangadhar

Abstract:

Objective: Impaired facial emotion recognition is widely reported in schizophrenia. Neuropeptide oxytocin is known to modulate brain regions involved in facial emotion recognition, namely amygdala, in healthy volunteers. However, its effect on facial emotion recognition deficits seen in schizophrenia is not well explored. In this study, we examined the effect of intranasal OXT on processing facial emotions and its neural correlates in patients with schizophrenia. Method: 12 male patients (age= 31.08±7.61 years, education= 14.50±2.20 years) participated in this single-blind, counterbalanced functional magnetic resonance imaging (fMRI) study. All participants underwent three fMRI scans; one at baseline, one each after single dose 24IU intranasal OXT and intranasal placebo. The order of administration of OXT and placebo were counterbalanced and subject was blind to the drug administered. Participants performed a facial emotion recognition task presented in a block design with six alternating blocks of faces and shapes. The faces depicted happy, angry or fearful emotions. The images were preprocessed and analyzed using SPM 12. First level contrasts comparing recognition of emotions and shapes were modelled at individual subject level. A group level analysis was performed using the contrasts generated at the first level to compare the effects of intranasal OXT and placebo. The results were thresholded at uncorrected p < 0.001 with a cluster size of 6 voxels. Neuropeptide oxytocin is known to modulate brain regions involved in facial emotion recognition, namely amygdala, in healthy volunteers. Results: Compared to placebo, intranasal OXT attenuated activity in inferior temporal, fusiform and parahippocampal gyri (BA 20), premotor cortex (BA 6), middle frontal gyrus (BA 10) and anterior cingulate gyrus (BA 24) and enhanced activity in the middle occipital gyrus (BA 18), inferior occipital gyrus (BA 19), and superior temporal gyrus (BA 22). There were no significant differences between the conditions on the accuracy scores of emotion recognition between baseline (77.3±18.38), oxytocin (82.63 ± 10.92) or Placebo (76.62 ± 22.67). Conclusion: Our results provide further evidence to the modulatory effect of oxytocin in patients with schizophrenia. Single dose oxytocin resulted in significant changes in activity of brain regions involved in emotion processing. Future studies need to examine the effectiveness of long-term treatment with OXT for emotion recognition deficits in patients with schizophrenia.

Keywords: recognition, functional connectivity, oxytocin, schizophrenia, social cognition

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191 Cycle-Oriented Building Components and Constructions Made from Paper Materials

Authors: Rebecca Bach, Evgenia Kanli, Nihat Kiziltoprak, Linda Hildebrand, Ulrich Knaack, Jens Schneider

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The building industry has a high demand for resources and at the same time is responsible for a significant amount of waste created worldwide. Today's building components need to contribute to the protection of natural resources without creating waste. This is defined in the product development phase and impacts the product’s degree of being cycle-oriented. Paper-based materials show advantage due to their renewable origin and their ability to incorporate different functions. Besides the ecological aspects like renewable origin and recyclability the main advantages of paper materials are its light-weight but stiff structure, the optimized production processes and good insulation values. The main deficits from building technology’s perspective are the material's vulnerability to humidity and water as well as inflammability. On material level, those problems can be solved by coatings or through material modification. On construction level intelligent setup and layering of a building component can improve and also solve these issues. The target of the present work is to provide an overview of developed building components and construction typologies mainly made from paper materials. The research is structured in four parts: (1) functions and requirements, (2) preselection of paper-based materials, (3) development of building components and (4) evaluation. As part of the research methodology at first the needs of the building sector are analyzed with the aim to define the main areas of application and consequently the requirements. Various paper materials are tested in order to identify to what extent the requirements are satisfied and determine potential optimizations or modifications, also in combination with other construction materials. By making use of the material’s potentials and solving the deficits on material and on construction level, building components and construction typologies are developed. The evaluation and the calculation of the structural mechanics and structural principals will show that different construction typologies can be derived. Profiles like paper tubes can be used at best for skeleton constructions. Massive structures on the other hand can be formed by plate-shaped elements like solid board or honeycomb. For insulation purposes corrugated cardboard or cellulose flakes have the best properties, while layered solid board can be applied to prevent inner condensation. Enhancing these properties by material combinations for instance with mineral coatings functional constructions mainly out of paper materials were developed. In summary paper materials offer a huge variety of possible applications in the building sector. By these studies a general base of knowledge about how to build with paper was developed and is to be reinforced by further research.

Keywords: construction typologies, cycle-oriented construction, innovative building material, paper materials, renewable resources

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190 Quantification of Global Cerebrovascular Reactivity in the Principal Feeding Arteries of the Human Brain

Authors: Ravinder Kaur

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Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

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189 Arthroscopic Fixation of Posterior Cruciate Ligament Avulsion Fracture through Posterior Trans Septal Portal Using Button Fixation Device: Mini Tight Rope

Authors: Ratnakar Rao, Subair Khan, Hari Haran

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Posterior cruciate ligament (PCL) avulsion fractures is a rare condition and commonly mismanaged.Surgical reattachment has been shown to produce better result compared with conservative management.Only few techniques are reported in arthroscopic fixation of PCL Avulsion Fracture and they are complex.We describe a new technique in fixation of the PCL Avulsion fracture through a posterior trans septal portal using button fixation device (Mini Tight Rope). Eighteen patients with an isolated posterior cruciate ligament avulsion fracture were operated under arthroscopy. Standard Antero Medial Portal and Antero Lateral portals made and additional Postero Medial and Postero Lateral portals made and trans Septal portal established. Avulsion fracture identified, elevated, prepared. Reduction achieved using PCL Tibial guide (Arthrex) and fixation was achieved using Mini Tight Rope,Arthrex (2 buttons with a suture). Reduction confirmed using probe and Image intensifier. Postoperative assessment made clinically and radiologically. 15 patients had good to excellent results with no posterior sag or instability. The range of motion was normal. No complications were recorded per operatively. 2 patients had communition of the fragment while drilling, for one patient it was managed by suturing technique and the second patient PCL Reconstruction was done. One patient had persistent instability with poor outcome. Establishing trans septal portal helps in better visualization of the posterior compartment of the knee. Assessment of the bony fragment, preparation 0f the bone bed andit protects from injury to posterior neurovascular structures. Fixation using the button with suture (Mini Tight Rope) is stable and easily reproducible for PCL Avulsion fracture with single large fragment.

Keywords: PCL avulsion, arthroscopy, transeptal, minitight rope technique

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188 Phonological Encoding and Working Memory in Kannada Speaking Adults Who Stutter

Authors: Nirmal Sugathan, Santosh Maruthy

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Background: A considerable number of studies have evidenced that phonological encoding (PE) and working memory (WM) skills operate differently in adults who stutter (AWS). In order to tap these skills, several paradigms have been employed such as phonological priming, phoneme monitoring, and nonword repetition tasks. This study, however, utilizes a word jumble paradigm to assess both PE and WM using different modalities and this may give a better understanding of phonological processing deficits in AWS. Aim: The present study investigated PE and WM abilities in conjunction with lexical access in AWS using jumbled words. The study also aimed at investigating the effect of increase in cognitive load on phonological processing in AWS by comparing the speech reaction time (SRT) and accuracy scores across various syllable lengths. Method: Participants were 11 AWS (Age range=19-26) and 11 adults who do not stutter (AWNS) (Age range=19-26) matched for age, gender and handedness. Stimuli: Ninety 3-, 4-, and 5-syllable jumbled words (JWs) (n=30 per syllable length category) constructed from Kannada words served as stimuli for jumbled word paradigm. In order to generate jumbled words (JWs), the syllables in the real words were randomly transpositioned. Procedures: To assess PE, the JWs were presently visually using DMDX software and for WM task, JWs were presented through auditory mode through headphones. The participants were asked to silently manipulate the jumbled words to form a Kannada real word and verbally respond once. The responses for both tasks were audio recorded using record function in DMDX software and the recorded responses were analyzed using PRAAT software to calculate the SRT. Results: SRT: Mann-Whitney test results demonstrated that AWS performed significantly slower on both tasks (p < 0.001) as indicated by increased SRT. Also, AWS presented with increased SRT on both the tasks in all syllable length conditions (p < 0.001). Effect of syllable length: Wilcoxon signed rank test was carried out revealed that, on task assessing PE, the SRT of 4syllable JWs were significantly higher in both AWS (Z= -2.93, p=.003) and AWNS (Z= -2.41, p=.003) when compared to 3-syllable words. However, the findings for 4- and 5-syllable words were not significant. Task Accuracy: The accuracy scores were calculated for three syllable length conditions for both PE and PM tasks and were compared across the groups using Mann-Whitney test. The results indicated that the accuracy scores of AWS were significantly below that of AWNS in all the three syllable conditions for both the tasks (p < 0.001). Conclusion: The above findings suggest that PE and WM skills are compromised in AWS as indicated by increased SRT. Also, AWS were progressively less accurate in descrambling JWs of increasing syllable length and this may be interpreted as, rather than existing as a uniform deficiency, PE and WM deficits emerge when the cognitive load is increased. AWNS exhibited increased SRT and increased accuracy for JWs of longer syllable length whereas AWS was not benefited from increasing the reaction time, thus AWS had to compromise for both SRT and accuracy while solving JWs of longer syllable length.

Keywords: adults who stutter, phonological ability, working memory, encoding, jumbled words

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187 Effect of Exercise and Mindfulness on Cognitive and Psycho-Emotional Functioning in Children with ADHD

Authors: Hannah Bigelow, Marcus D. Gottlieb, Michelle Ogrodnik, Jeffrey, D. Graham, Barbara Fenesi

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Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders affecting approximately 6% of children worldwide. ADHD is characterized by a combination of persistent deficits including impaired inhibitory control, working memory and task-switching. Many children with ADHD also have comorbid mental health issues such as anxiety and depression. There are several treatment options to manage ADHD impairments, including drug and behavioural management therapy, but they all have drawbacks, such as worsening mood disturbances or being inaccessible to certain demographics. Both physical exercise and mindfulness meditation serve as alternative options to potentially help mitigate ADHD symptoms. Although there is extensive support for the benefits of long-term physical exercise or mindfulness meditation programs, there is insufficient research investigating how acute bouts (i.e., single, short bouts) can help children with ADHD. Thus, the current study aimed to understand how single, short bouts of exercise and mindfulness meditation impacts executive functioning and psycho-emotional well-being in children with ADHD, as well as to directly compare the efficacy of these two interventions. The study used a a pre- post-test, within-subjects design to assess the effects of a 10-minute bout of moderate intensity exercise versus a 10-minute bout of mindfulness meditation (versus 10 minutes of a reading control) on the executive functioning and psycho-emotional well-being of 16 children and youth with ADHD aged 10-14 (male=11; White=80%). Participants completed all three interventions: 10 minutes of exercise, 10 minutes of mindfulness meditation, and 10 minutes of reading (control). Executive functioning (inhibitory control, working memory, task-switching) and psycho-emotional well-being (mood, self-efficacy) were assessed before and after each intervention. Mindfulness meditation promoted executive functioning, while exercise enhanced positive mood and self-efficacy. Critically, this work demonstrates that a single, short bout of mindfulness meditation session can promote inhibitory control among children with ADHD. This is especially important for children with ADHD as inhibitory control deficits are among the most pervasive challenges that they face. Furthermore, the current study provides preliminary evidence for the benefit of acute exercise for promoting positive mood and general self-efficacy for children and youth with ADHD. These results may increase the accessibility of acute exercise for children with ADHD, providing guardians and teachers a feasible option to incorporate just 10 minutes of exercise to assist children emotionally. In summary, this research supports the use of acute exercise and mindfulness meditation on varying aspects of executive functioning and psycho-emotional well-being in children and youth with ADHD. This work offers important insight into how behavioural interventions could be personalized according to a child’s needs.

Keywords: attention-deficit hyperactivity disorder (ADHD), acute exercise, mindfulness meditation, executive functioning, psycho-emotional well-being

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186 Teaching Children With Differential Learning Needs By Understanding Their Talents And Interests

Authors: Eunice Tan

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The purpose of this presentation is to look at an alternative to the approach and methodologies of working with special needs. The strength-based approach to education embodies a paradigm shift. It is a strategy to move away from a deficit-based methodology which inadvertently may lead to an extensive list of things that the child cannot do or is unable to do. Today, many parents of individuals with special needs are focused on the child’s deficits rather than on his or her strengths. Even when parents Recognise and identify their child’s strengths to be valuable and wish to develop their abilities, they face the challenge that there are insufficient programs committed to supporting the development and improvement of such abilities. What is a strength-based approach in education? A strength-based approach in education focuses on students' positive qualities and contributions to class instead of the skills and abilities they may not have. Many schools are focused on the child’s special educational needs rather than the whole child. Parents interviewed have said that they have to engage external tutors to help hone in on their child’s interests and strengths.

Keywords: differential learning needs, special needs, instructional style, talents

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185 Alwadei Syndrome - A Genetic Cause Of Intellectual Disability

Authors: Mafalda Moreira, Diana Alba, Inês Paiva Ferreira, Rita Calejo, Ana Rita Soares, Leonilde Machado

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Intellectual disability (ID) is characterized by deficits in intellectualfunctioningassociatedwithalterations in the adaptive behaviour, whose onset is inthedevelopmentalperiod. Itaffects 3% of the population, ofwhich 10% have a geneticaetiology. One of those causes isAlwadeiSyndrome, with 3 cases describedworldwide. It results from a homozygous nonsense mutation in theRUSC2 gene andisassociatedwithintellectualdisabilityanddysmorphic facialfeatures. Theauthorsreportthe case of a 5-year-old-boy, born to a healthymotherafter a full-termuneventfulpregnancy, thatwasreferred to Neurodevelopmentalconsultationdue toglobal developmentaldelay. Familyhistoryrevealedlearningdifficulties in the paternal brotherhood. Milddismorphicfeatureswereevidentsuch as darkinfraorbitalregion, low-set ears, beakednose, retrognathism, high-archedpalateandjointhyperlaxity. WechslerIntelligenceScale for Children III fullscaleIQ quoted 61. Karyotypeandchromosomalmicroarrayanalysiswerenormal, as well as the fragile X molecular study. DNA sequencingwasthenperformedandallowedtheidentificationof amutation in the RUSC2 gene. Theetiologicaldiagnosisof ID remains unknown in up to 80% of cases, creatinguncertainty in children’sfamilies. Theadvances in DNA sequencingtechnologieshaveincreasedourknowledgeofthegeneticdiseasesinvolved, as theAlwadeisyndromewasonlydescribedsince 2016. Thegeneticdiagnosisof ID allowsfamilygeneticcounselingandenablesthedevelopmentof target therapeutic approaches.

Keywords: intellectual disability, genetic aetiology, alwadei syndrome, RUSC2

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184 Variation in Youth and Family Experiences of System of Care Principles in Community Mental Health

Authors: James D. Beauchemin

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This study tested whether youth mental health care quality, operationalized as the extent to which youth and families experienced system-of-care principles in service interactions with providers, varied by level of youth need after adjusting for sociodemographic and treatment factors. The relationship of quality to clinical outcomes was also examined. Using administrative data and cross-sectional surveys from a stratified random sample of 1,124 caregivers of youths ages 5 to 20 within a statewide system-of-care, adjusted analyses indicated youths with the most intensive needs were significantly less likely to experience high-quality care (51% vs. 63%, p=0.016), with marked deficits on 6 of 9 items. Receipt of lower-quality care predicted less improvement in youth functioning. Despite considerable effort to develop systems-of-care for youths with the most severe mental health needs, these data suggest quality disparities remain for the most impaired youths. Policy and intervention development may be needed to improve the quality of care for this population.

Keywords: system-of-care, adherence, mental health, youth

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183 Determination of Some Biochemical Parameters in Women during the First Trimester of Pregnancy (Normal Pregnancy and Missed Miscarriage)

Authors: M. Yahia, N. Chaoui, A. Chaouch, Massinissa Yahia

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Our study was designed to determine the metabolic changes of some biochemical parameters (cholesterol, triglyceride, Iron, uric acid, Urea and folic acid) and highlight their changes in 57 women of the region Batna, during the first trimester of pregnancy. This practical work was done with 27 women with missed miscarriage, compared with 30 control subjects of normal pregnant women. The assay results revealed a highly significant difference (P = 0.0006) between the two groups in serum iron (64.00 vs 93.54) and in the rate of folate (6.70 vs 9.22) (P <0.001) but no difference was found regarding the rate of Ca (9.69 vs 10.20), urea (0.19 vs 0.17), UA (33.96 vs 32.76), CH (1.283 vs 1.431), and TG (0.8852 vs 0.8290). The present study indicates that iron deficiency and folate are associated with missed miscarriage, but no direct pathophysiological link has been determined. Further in-depth studies are needed to determine the exact mechanism by which these deficits lead to a missed miscarriage.

Keywords: biochemical parameters, pregnant women, missed miscarriage, Algeria

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182 Posterior Circulation Ischemic Strokes in Olympic and Division 1 Wrestlers

Authors: Christen Kutz

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Objective: The aim of this study is to review a case series of 4 high-level Olympic and Division 1 wrestlers who experienced debilitating posterior circulation ischemic strokes during or after a competitive wrestling event and to identify risk factors, etiology and outcomes of stroke in young, healthy elite wrestlers. Background: Stroke occurs in one in 10,000 people under age 64. In young adults, the most common causes of stroke are cardiac embolism, hypercoagulable state, and vasculopathy. One-third of these strokes occur in young, fit individuals. There is little published literature about ischemic strokes that occur in wrestlers. Based on the nature of wrestling, the risk of injury or dissection to neurovascular structures may be a possible theory, but very few case reports exist. Methodology: 4 wrestlers under the age of 44 with a known history of ischemic stroke participated in individual interviews either in person or virtually. Each of the wrestlers provided their demographic information, wrestling background, clinical presentation at the time of stroke, imaging results, identification of potential risk factors, acute treatment and recovery. Results: 3 white male Division 1 wrestlers (2 Lehigh University, 1 Lock Haven University) and 1 black male 2008 Olympian experienced posterior circulation strokes. Case #1 felt a “pop” while wrestling (lateral medullary infarct, possible vertebral artery dissection); Case #2 awoke with severe vertigo, sweating, and vomiting after wrestling the previous day (left cerebellar infarct, (+) protein S deficiency); Case #3 severe vertigo, ataxia, and sensation of impending doom after wrestling earlier that week (left cerebellar infarct, hypoplastic left vertebral artery (+) anti-cardiolipin antibodies). Case #4 severe dizziness, confusion (left cerebellar stroke, vertebral artery dissection, small PFO). Conclusion: 3 wrestlers were started on anti-platelet therapy, risk factors were modified, and returned to their sport. 1 wrestler was placed on anti-coagulation and retired from competition.

Keywords: stroke, wrestling, Olympic, posterior circulation

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181 The Age Difference in Social Skills Constructs for School Adaptation: A Cross-Sectional Study of Japanese Students at Elementary, Junior, and Senior High School

Authors: Hiroki Shinkawa, Tadaaki Tomiie

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Many interventions for social skills acquisition aim to decrease the gap between social skills deficits in the individual and normative social skills; nevertheless little is known of typical social skills according to age difference in students. In this study, we developed new quintet of Hokkaido Social Skills Inventory (HSSI) in order to identify age-appropriate social skills for school adaptation. First, we selected 13 categories of social skills for school adaptation from previous studies, and created questionnaire items through discussion by 25 teachers in all three levels from elementary schools to senior high schools. Second, the factor structures of five versions of the social skills scale were investigated on 2nd grade (n = 1,864), 4th grade (n = 1,936), 6th grade (n = 2,085), 7th grade (n = 2,007), and 10th grade (n = 912) students, respectively. The exploratory factor analysis showed that a number of constructing factors of social skills increased as one’s grade in school advanced. The results in the present study can be useful to characterize the age-appropriate social skills for school adaptation.

Keywords: social skills, age difference, children, adolescents

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180 Literature Review: The Efficacy of Play-Based Therapy Programs in Decreasing Core Symptoms of Autism Spectrum Disorder

Authors: Rozan El-Khateeb

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This literature review examines the effectiveness of therapy programs that utilize play as an intervention for reducing symptoms associated with Autism Spectrum Disorder (ASD). Play-based therapy approaches provide a child-centered and developmentally appropriate framework to address the core symptoms of ASD, including social communication deficits, restricted and repetitive behaviors, and sensory sensitivities. The review explores various play-based therapy strategies and their impact on improving social skills, communication abilities, adaptive behaviors, and overall functioning in individuals with ASD. The findings suggest that play-based therapy programs hold promise as effective interventions for reducing symptoms and enhancing the quality of life for individuals with ASD. However, further research is necessary to establish standardized protocols, identify optimal dosage and duration, and evaluate long-term outcomes.

Keywords: autism, ABA, play, NET, systematic review

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179 Reading Comprehension in Profound Deaf Readers

Authors: S. Raghibdoust, E. Kamari

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Research show that reduced functional hearing has a detrimental influence on the ability of an individual to establish proper phonological representations of words, since the phonological representations are claimed to mediate the conceptual processing of written words. Word processing efficiency is expected to decrease with a decrease in functional hearing. In other words, it is predicted that hearing individuals would be more capable of word processing than individuals with hearing loss, as their functional hearing works normally. Studies also demonstrate that the quality of the functional hearing affects reading comprehension via its effect on their word processing skills. In other words, better hearing facilitates the development of phonological knowledge, and can promote enhanced strategies for the recognition of written words, which in turn positively affect higher-order processes underlying reading comprehension. The aims of this study were to investigate and compare the effect of deafness on the participants’ abilities to process written words at the lexical and sentence levels through using two online and one offline reading comprehension tests. The performance of a group of 8 deaf male students (ages 8-12) was compared with that of a control group of normal hearing male students. All the participants had normal IQ and visual status, and came from an average socioeconomic background. None were diagnosed with a particular learning or motor disability. The language spoken in the homes of all participants was Persian. Two tests of word processing were developed and presented to the participants using OpenSesame software, in order to measure the speed and accuracy of their performance at the two perceptual and conceptual levels. In the third offline test of reading comprehension which comprised of semantically plausible and semantically implausible subject relative clauses, the participants had to select the correct answer out of two choices. The data derived from the statistical analysis using SPSS software indicated that hearing and deaf participants had a similar word processing performance both in terms of speed and accuracy of their responses. The results also showed that there was no significant difference between the performance of the deaf and hearing participants in comprehending semantically plausible sentences (p > 0/05). However, a significant difference between the performances of the two groups was observed with respect to their comprehension of semantically implausible sentences (p < 0/05). In sum, the findings revealed that the seriously impoverished sentence reading ability characterizing the profound deaf subjects of the present research, exhibited their reliance on reading strategies that are based on insufficient or deviant structural knowledge, in particular in processing semantically implausible sentences, rather than a failure to efficiently process written words at the lexical level. This conclusion, of course, does not mean to say that deaf individuals may never experience deficits at the word processing level, deficits that impede their understanding of written texts. However, as stated in previous researches, it sounds reasonable to assume that the more deaf individuals get familiar with written words, the better they can recognize them, despite having a profound phonological weakness.

Keywords: deafness, reading comprehension, reading strategy, word processing, subject and object relative sentences

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178 Intraventricular Hemorrhage Caused by Subarachnoid Hemorrhage; When Time Is Life

Authors: Devieta Romadhon Saendardy

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Introduction: The case of aneurysmal subarachnoid hemorrhage (SAH) associated with intraventricular hemorrhage (IVH) in many way. In general, the anterior communicating artery and posterior circulation aneurysms cause Intraventricular Hemorrhage. The development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Case: This case report presents a 51-year-old female patient who developed IVH following SAH. The patient's Glasgow Coma Scale score was 14, the patient has a severe headache, and there were right extremity hemipharese neurological deficits. A non-contrast head CT scan revealed a massive intraventricular haemorrhage. In an hour, the patient got her headache and pharese worse. Discussion: Intraventricular hemorrhage is a serious complication of subarachnoid hemorrhage, necessitating prompt recognition and management. This case highlights the importance of a time management, medical management and surgical intervention to optimize outcomes in patients with intraventricular hemorrhage caused by subarachnoid hemorrhage. Placement of a shunt system improves clinical outcome in intraventricular hemorrhage.

Keywords: Intraventricular hemorrhage, subarachnoid hemorrhage, shunt, time

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177 A Case Study of Meningoencephalitis following Le Fort I Osteotomy

Authors: Ryan Goh, Nicholas Beech

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Introduction: Le Fort I Osteotomies, although are common procedures in Oral and Maxillofacial Surgery, carry a degree of risk of unfavourable propagation of the down-fracture of the maxilla. This may be the first reported case in the literature for meningoencephalitis to occur following a Le Fort I Osteotomy. Case: A 32-year-old female was brought into the Emergency Department four days after a Le Fort I Osteotomy, with a Glasgow Coma Scale (GCS) of 8 (E3V1M4). A Computed Tomography (CT) Head showed a skull base fracture at the right sphenoid sinus. Lumbar puncture was completed, and Klebsiella oxytoca was found in the Cerebrospinal Fluid (CSF). She was treated with Meropenem, and rapidly improved thereafter. CSF rhinorrhoea was identified when she was extubated, which was successfully managed via a continuous lumbar drain. She was discharged on day 14 without any neurological deficits. Conclusion: The most likely aspect of the Le Fort I Osteotomy to obtain a skull base fracture is during the pterygomaxillary disjunction. Care should always be taken to avoid significant risks of skull base fractures, CSF rhinorrhoea, meningitis and encephalitis.

Keywords: meningitis, orthognathic surgery, post-operative complication, skull base, rhinorrhea

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176 Assessment of Neurodevelopmental Needs in Duchenne Muscular Dystrophy

Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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175 Rumination in Borderline Personality Disorder: A Meta-Analytic Review

Authors: Mara J. Richman, Zsolt Unoka, Robert Dudas, Zsolt Demetrovics

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Borderline personality disorder (BPD) is characterized by deficits in emotion regulation and effective liability. Of this domain, ruminative behaviors have been considered a core feature of emotion dysregulation difficulties. Taking this into consideration, a meta-analysis was performed to assess how BPD symptoms correlate with rumination, while also considering clinical moderator variables such as comorbidity, GAF score, and type of BPD symptom and demographic moderator variables such as age, gender, and education level. Analysis of correlation across rumination domains for the entire sample revealed a medium overall correlation. When assessing types of rumination, the largest correlation was among pain rumination followed by anger, depressive, and anxious rumination. Furthermore, affective instability had the strongest correlation with increased rumination, followed by unstable relationships, identity disturbance, and self-harm/ impulsivity, respectively. Demographic variables showed no significance. Clinical implications are considered and further therapeutic interventions are discussed in the context of rumination.

Keywords: borderline personality disorder, meta-analysis, rumination, symptoms

Procedia PDF Downloads 177
174 Dimethyl fumarate Alleviates Valproic Acid-Induced Autism in Wistar Rats via Activating NRF-2 and Inhibiting NF-κB Pathways

Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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