Search results for: brain adaptation

Authors: V. A. Doss, R. Sowndarya, K. Juila Rose Mary

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Objective: Amino acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. The objective of the present study was to identify the amino acids as possible metabolite biomarkers for depression using GCMS (Gas Chromatography Mass Spectrometry) before and after exercise regimen in brain samples of depression induced animal models. Methods: Depression-like behaviour was induced by Chronic Unpredictable mild stress (CUMS). Severity of depression was measured by forced swim test (FST) and sucrose consumption test (SCT). Swimming protocol was followed for 4 weeks of exercise treatment. Brain obtained from depressed and exercise treated rats were used for the metabolite analysis by GCMS. Subsequent statistical analysis obtained by ANOVA followed by post hoc test revealed significant metabolic changes. Results: Amino acids such as alanine, glycine, serine, glutamate, homocysteine, proline and branched chain aminoacids (BCAs) Leucine, Isoleucine, Valine were determined in brain samples of control, depressed and exercised groups. Among these amino acids, the levels of D-Serine and branched chain amino acids were found to be decreased in depression induced rats. After four weeks of swimming exercise regimen, there were improvements in the levels of serine and Branched chain amino acids. Conclusion: We suggest that Serine and BCAs may be investigated as potential metabolite markers using GCMS and their beneficial metabolic changes in Exercise.

Keywords: metabolomics, depression, forced swim test, exercise, amino acid metabolites, GCMS, biomarker

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Authors: Edwin Forero-Garcia, Jaime Vitola, Brayan Cardenas, Johan Casagua

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This research article presents the integration of electronic and computer systems, which developed an ultrasonic signal processing system that performs the capture, adaptation, and analog-digital conversion to later carry out its processing and visualization. The capture and adaptation of the signal were carried out from the design and implementation of an analog electronic system distributed in stages: 1. Coupling of impedances; 2. Analog filter; 3. Signal amplifier. After the signal conditioning was carried out, the ultrasonic information was digitized using a digital microcontroller to carry out its respective processing. The digital processing of the signals was carried out in MATLAB software for the elaboration of A-Scan, B and D-Scan types of ultrasonic images. Then, advanced processing was performed using the SAFT technique to improve the resolution of the Scan-B-type images. Thus, the information from the ultrasonic images was displayed in a user interface developed in .Net with Visual Studio. For the validation of the system, ultrasonic signals were acquired, and in this way, the non-invasive inspection of the structures was carried out and thus able to identify the existing pathologies in them.

Keywords: acquisition, signal processing, ultrasound, SAFT, HMI

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Authors: Safieh Javadinejad

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In order to make well-informed decisions respecting long-term system planning, resource managers and policy creators necessitate to comprehend the interconnections among energy and water utilization and manufacture—and also the energy-water nexus. Planning and assessment issues contain the enhancement of strategies for declining the water and energy system’s vulnerabilities to climate alteration with also emissions of decreasing greenhouse gas. In order to deliver beneficial decision support for climate adjustment policy and planning, understanding the regionally-specific features of the energy-water nexus, and the history-future of the water and energy source systems serving is essential. It will be helpful for decision makers understand the nature of current water-energy system conditions and capacity for adaptation plans for future. This research shows an integrated hydrology/energy modeling platform which is able to extend water-energy examines based on a detailed illustration of local circumstances. The modeling links the Water Evaluation and Planning (WEAP) and the Long Range Energy Alternatives Planning (LEAP) system to create full picture of water-energy processes. This will allow water managers and policy-decision makers to simply understand links between energy system improvements and hydrological processing and realize how future climate change will effect on water-energy systems. The Zayandeh Rud river basin in Iran is selected as a case study to show the results and application of the analysis. This region is known as an area with large integration of both the electric power and water sectors. The linkages between water, energy and climate change and possible adaptation strategies are described along with early insights from applications of the integration modeling system.

Keywords: climate impacts, hydrology, water systems, adaptation planning, electricity, integrated modeling

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Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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Authors: Angelis P. Barlampas

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Purpose: A 29 years old woman presented in the emergency department with psychiatric symptoms. The psychiatrist ordered a computed tomography scan as part of a general examination. Material and methods: The CT showed bilateral enlarged choroid plexus structures mimicking papillomata and situated in the trigones of the lateral ventricles. The left choroid plexus was heavily calcified, but the right one has no any obvious calcifications. Results: It is well kown that any brain mass can present with behavioral changes and even psychiatric symptomatology. Papillomata of the ventricular system have been described to cause psychotic episodes. According to literature, choroid plexus papillomas are seldom neuroepithelial intraventricular tumors, which are benign and categorized as WHO grade 1 tumors. They are more common in the pediatric population, but they can occur in the adults, too1. In addition, the distinction between choroid plexus papilloma and carcinoma is very difficult and impossible by imagine alone. It can only be implied with more advanced imaging, such as arterial spin labeling and MRI. The final diagnosis is, of course, after surgical excision. The usual location in adults is the fourth ventricle, but in children, it is the lateral ventricles. Their imaging appearance is that of a solid vascular tumor, which enhances intensely after the intravenous administration of contrast material. One out of fourth tumors presents speckled calcifications1. In our case, there are symmetrically sized masses at the trigones, and there are no calcifications in one of them, whereas the other one is grossly calcified. Also, there is no obvious hydrocephalus or any other evidence of increased intracranial pressure. General conclusions: When there is a new psychiatric patient, someone must undergo any possible examination, and of course, a brain CT study should be done to exclude any rare organic causes that may be responsible for the disease.

Keywords: phycosis, intraventricular masses, CT, brain calcifications

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Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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Authors: K. C. Wong

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This paper demonstrates a number of examples in the hope to shed some light on the possibility of designing future operating systems in a more adaptation-based manner. A modern operating system, we conceive, should possess the capability of 'learning' in such a way that it can dynamically adjust its services and behavior according to the current status of the environment in which it operates. In other words, a modern operating system should play a more proactive role during the session of providing system services to users. As such, a modern operating system is expected to create a computing environment, in which its users are provided with system services more matching their dynamically changing needs. The examples demonstrated in this paper show that user's resource access patterns 'learned' and determined during a session can be utilized to improve system performance and hence to provide users with a better and more effective computing environment. The paper also discusses how to use the frequency, the continuity, and the duration of resource accesses in a session to quantitatively measure and determine user's resource access patterns for the examples shown in the paper.

Keywords: adaptation-based systems, operating systems, resource access patterns, system performance

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Authors: Zain Khan, Steve Ahn, Kathy Monypenny, James Fink

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In Australian public hospitals, there were approximately 34,000 reported inpatient falls between 2015 to 2016. The gold standard for diagnosing intracranial injury is non-contrast enhanced brain computed tomography (CTB). Over a three-month timeframe, a total of one hundred and eighty (180) falls were documented between the hours of 4pm and 8am at a large metro hospital. Only three (3) of these scans demonstrated a positive intra-cranial finding. The rationale for scanning varied. The common indications included a fall with head strike, the presence of blood thinning medication, loss of consciousness, reduced Glasgow Coma Scale (GCS), vomiting and new neurological findings. There are several validated tools to aid in decision-making around ordering CTB scans in the acute setting, but no such accepted tool exists for the inpatient space. With further data collection, spanning a greater length of time and through involving multiple centres, work can be done towards generating such a tool that can be utilized for inpatient falls.

Keywords: computed tomography, falls, inpatient, intracranial hemorrhage

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: Evangelos G. Karvelas, Christos Liosis, Andreas Theodorakakos, Theodoros E. Karakasidis

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In the present work, a numerical method for the estimation of the appropriate gradient magnetic fields for optimum driving of the particles into the desired area inside the human body is presented. The proposed method combines Computational Fluid Dynamics (CFD), Discrete Element Method (DEM) and Covariance Matrix Adaptation (CMA) evolution strategy for the magnetic navigation of nanoparticles. It is based on an iteration procedure that intents to eliminate the deviation of the nanoparticles from a desired path. Hence, the gradient magnetic field is constantly adjusted in a suitable way so that the particles’ follow as close as possible to a desired trajectory. Using the proposed method, it is obvious that the diameter of particles is crucial parameter for an efficient navigation. In addition, increase of particles' diameter decreases their deviation from the desired path. Moreover, the navigation method can navigate nanoparticles into the desired areas with efficiency approximately 99%.

Keywords: computational fluid dynamics, CFD, covariance matrix adaptation evolution strategy, discrete element method, DEM, magnetic navigation, spherical particles

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Authors: Fatimah A. Alhomaid, Nadia H. Mahmoud, Maha A. Al-Qaraawi

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The present study was designed to induce hyperhomocysteinemia (HHcy) in elderly male and female rats. Also,to evaluate, the effect of (HHcy) as a risk factor for cerebrovascular disease and brain atrophy and folate supplementation on serum levels of Hcy, total cholesterol, low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides, pyridoxal phosphate , folate also, histopathological examination of brain and cerebrovascular vessels In this work 50 male and 50 female elderly albino rats were used and divided into five groups. The first group served as control, the second and third group received two different dose of L-methionine, the fourth and fifth group received fortified diet with folate powder plus L-methionine. Our results showed that homocysteine levels in male and female rats that received low and high dose of methionine were higher than in the control group, while the levels of folate significantly decreased in male rats only. Induced hyperhomocysteinemia in elderly male and female rats led to significant increase in serum level of cholesterol, LDLc and triglycerides but serum level of HDLc were significantly lower in methionine treated male and female rats than in control. Our results showed that a strong positive correlation between all these parameters and homocysteine except HDLc levels which correlate negatively to Hcy levels. Administration of folate to methionine treated male rats led to insignificant changes in the level of cholesterol when compared to control group but this level was found to be significantly decrease in female rats received small dose of methionine. When the level of cholesterol compared to the same dose of methionine treated group we found a significant decrease in both male and female rats. LDLc and triglycerides level significantly decrease in male rats only versus the control rats, while when compared to low and high dose of methionine a significant decreased occurs. A significant increase in serum level of HDLc in male and female rats when compared to both control and methionine treated groups. In male and female rats supplemented with folate we found an increased serum levels of folate when compared to rats received both dose of methionine. The levels of pyridoxal phosphate significantly decreased in all treated rats compared to the control group and its level were increased with supplementation of folate versus the rats received small and large dose of methionine. It can be concluded that hyperhomocysteinemia may be an additional risk factor for cerebrovascular atherosclesosis and brain atrophy in elderly people and diatery supplementation with folate blocking the activity of homocysteine and may be considered as a therapeutic possibility.

Keywords: hyperhomocysteinemia, brain atrophy, cerebrovascular, L-methionine, pyridoxal phosphate

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Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

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Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

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Authors: Jacqueline Żammit

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Recent research indicates that the utilization of right-brain strategies holds significant implications for the acquisition of language skills. Nevertheless, the utilization of visual culture as a means to stimulate these strategies and amplify language retention among adults engaging in second language (L2) learning remains a relatively unexplored area. This investigation delves into the impact of visual culture on activating right-brain processes during the initial stages of language acquisition, particularly in the context of teaching Maltese as a second language (ML2) to adult learners. By employing a qualitative research approach, this study convenes a focus group comprising twenty-seven educators to delve into a range of visual culture techniques integrated within language instruction. The collected data is subjected to thematic analysis using NVivo software. The findings underscore a variety of impactful visual culture techniques, encompassing activities such as drawing, sketching, interactive matching games, orthographic mapping, memory palace strategies, wordless picture books, picture-centered learning methodologies, infographics, Face Memory Game, Spot the Difference, Word Search Puzzles, the Hidden Object Game, educational videos, the Shadow Matching technique, Find the Differences exercises, and color-coded methodologies. These identified techniques hold potential for application within ML2 classes for adult learners. Consequently, this study not only provides insights into optimizing language learning through specific visual culture strategies but also furnishes practical recommendations for enhancing language competencies and skills.

Keywords: visual culture, right-brain strategies, second language acquisition, maltese as a second language, visual aids, language-based activities

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Authors: Zoran Barac, Maja Martinovic

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Higher Education Institutions (HEIs) are a special kind of organization, with its unique purpose and combination of actors. From the societal point of view, they are central institutions in the society that are involved in the activities of education, research, and innovation. At the same time, their societal function derives complex relationships between involved actors, ranging from students, faculty and administration, business community and corporate partners, government agencies, to the general public. HEIs are also particularly interesting as objects of governance research because of their unique public purpose and combination of stakeholders. Furthermore, they are the special type of institutions from an organizational viewpoint. HEIs are often described as “loosely coupled systems” or “organized anarchies“ that implies the challenging nature of their governance models. Governance models of HEIs describe roles, constellations, and modes of interaction of the involved actors in the process of strategic direction and holistic control of institutions, taking into account each particular context. Many governance models of the HEIs are primarily based on the balance of power among the involved actors. Besides the actors’ power and influence, leadership style and environmental contingency could impact the governance model of an HEI. Analyzing them through the frameworks of institutional and contingency theories, HEI governance models originate as outcomes of their institutional and contingency adaptation. HEIs tend to fit to institutional context comprised of formal and informal institutional rules. By fitting to institutional context, HEIs are converging to each other in terms of their structures, policies, and practices. On the other hand, contingency framework implies that there is no governance model that is suitable for all situations. Consequently, the contingency approach begins with identifying contingency variables that might impact a particular governance model. In order to be effective, the governance model should fit to contingency variables. While the institutional context creates converging forces on HEI governance actors and approaches, contingency variables are the causes of divergence of actors’ behavior and governance models. Finally, an HEI governance model is a balanced adaptation of the HEIs to the institutional context and contingency variables. It also encompasses roles, constellations, and modes of interaction of involved actors influenced by institutional and contingency pressures. Actors’ adaptation to the institutional context brings benefits of legitimacy and resources. On the other hand, the adaptation of the actors’ to the contingency variables brings high performance and effectiveness. HEI governance models outlined and analyzed in this paper are collegial, bureaucratic, entrepreneurial, network, professional, political, anarchical, cybernetic, trustee, stakeholder, and amalgam models.

Keywords: governance, governance models, higher education institutions, institutional context, situational context

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Authors: Singh Deepeshwar, Suhas Vinchurkar

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Similar to neuroimaging findings through functional magnetic resonance imaging (fMRI) assessing regional cerebral blood oxygenation, the functional near infrared spectroscopy (fNIRS) has also been used to assess hemodynamic responses in the imaged region of the brain. The present study assessed hemodynamic responses in terms of changes in oxygenation (HbO), deoxygenation (HbR) and total hemoglobin (THb) on the prefrontal cortex (PFC), bilaterally, using fNIRS in 10 participants who performed three voluntary regulated breathing (pranayama) practices viz. (i) Left nostril breathing (LNB), (ii) Right nostril breathing (RNB); and (iii) Alternating nostril breathing (ANB) and compared with normal breathing as baseline (BS). For this, we used 64 channel NIRS system covering left and the right prefrontal cortex. The normal breathing kept as baseline (BS) measures as regressors in the investigation of hemodynamic responses when compared with LNB, RNB and ANB. In the results, we found greater oxygenation in contralateral side i.e., higher activation on the left prefrontal cortex (lPFC) during RNB, and right prefrontal cortex (rPFC) during LNB, whereas ANB showed greater deoxygenation responses on both sides of PFC. Interestingly, LNB showed increased oxygenation on ipsilateral side i.e., lPFC but not during RNB. This suggests that voluntary regulated breathing produced an immediate effect not only on contralateral but ipsilateral sides of the brain as well. In conclusion, breathing practices are tightly coupled to cerebral rhythms of alternating cerebral hemispheric activity during particular nostril breathing. These results of the specific nostril breathing do not support previous findings of contralateral hemispheric improvement while left or right nostril breathing only.

Keywords: hemodynamic responses, brain, pranayama, voluntary regulated breathing practices, prefrontal cortex

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Authors: A. Alli-Oluwafuyi, A. Amin, S. M. Fii, S. O. Amusa, A. Imam, N. T. Asogwa, W. I. Abdulmajeed, F. Olaseinde, B. V. Owoyele

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Chronic stress or prolonged glucocorticoid administration impairs higher cognitive functions in rodents and humans. However, the mechanisms are not fully clear. Insulin and receptors are expressed in the brain and are involved in cognition. Insulin resistance accompanies Alzheimer’s disease and associated cognitive decline. The goal of this study was to evaluate the effects of sub-chronic administration of a glucocorticoid, dexamethasone (DEX) on behavior and biochemical changes in prefrontal cortex (PFC). Male Wistar rats were administered DEX (2, 4 & 8 mg/kg, IP) or saline for seven consecutive days and behavior was assessed in the following paradigms: “Y” maze, elevated plus maze, Morris’ water maze and novel object recognition (NOR) tests. Insulin, lactate dehydrogenase (LDH) and Superoxide Dismutase (SOD) activity were evaluated in homogenates of the prefrontal cortex. DEX-treated rats exhibited impaired prefrontal cortex function manifesting as reduced locomotion, impaired novel object exploration and impaired short- and long-term spatial memory compared to normal controls (p < 0.05). These effects were not consistently dose-dependent. These behavioral alterations were accompanied by a decrease in insulin concentration observed in PFC of 4 mg/kg DEX-treated rats compared to control (10μIU/mg vs. 50μIU/mg; p < 0.05) but not 2mg/kg. Furthermore, we report a modification of brain stress markers LDH and SOD (p > 0.05). These results indicate that prolonged activation of GCs disrupt prefrontal cortex function which may be related to insulin impairment. These effects may not be attributable to a non-specific elevation of oxidative stress in the brain. Future studies would evaluate mechanisms of GR-induced insulin loss.

Keywords: dexamethasone, insulin, memory, prefrontal cortex

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Authors: Mamadou Diop, Florence Crick, Momadou Sow, Kate Elizabeth Gannon

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Understanding SME leaders’ responses to climate is essential to cope with ongoing changes in temperature and rainfall. This study analyzes the response of SME leaders to the adverse effects of climate change in semi-arid lands (SAL) in Senegal. Based on surveys administrated to 161 SME leaders, this research shows that 91% of economic units are affected by climatic conditions, although 70% do not have a plan to deal with climate risks. Economic actors have striven to take measures to adapt. However, their efforts are limited by various obstacles accentuated by a lack of support from public authorities. In doing so, substantial political, institutional and financial efforts at national and local levels are needed to promote an enabling environment for economic actors to adapt. This will focus on information and training about the threats and opportunities related to global warming, the creation of an adaptation support fund to support local initiatives and the improvement of the institutional, regulatory and political framework.

Keywords: small and medium-sized enterprises, climate change, adaptation, semi-arid lands

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Authors: Suehyun Cho, Darrell Harrington, Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Alex Kiselyov, Michael Shpigelmacher

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Bionaut Labs, LLC is developing a minimally invasive robotic microdevice designed to treat non-communicating hydrocephalus in both adult and pediatric patients. The device utilizes biocompatible microsurgical particles (Bionaut™) that are specifically designed to safely and reliably perform accurate fenestration(s) in the 3rd ventricle, aqueduct of Sylvius, and/or trapped intraventricular cysts of the brain in order to re-establish normal cerebrospinal fluid flow dynamics and thereby balance and/or normalize intra/intercompartmental pressure. The Bionaut™ is navigated to the target via CSF or brain tissue in a minimally invasive fashion with precise control using real-time imaging. Upon reaching the pre-defined anatomical target, the external driver allows for directing the specific microsurgical action defined to achieve the surgical goal. Notable features of the proposed protocol are i) Bionaut™ access to the intraventricular target follows a clinically validated endoscopy trajectory which may not be feasible via ‘traditional’ rigid endoscopy: ii) the treatment is microsurgical, there are no foreign materials left behind post-procedure; iii) Bionaut™ is an untethered device that is navigated through the subarachnoid and intraventricular compartments of the brain, following pre-designated non-linear trajectories as determined by the safest anatomical and physiological path; iv) Overall protocol involves minimally invasive delivery and post-operational retrieval of the surgical Bionaut™. The approach is expected to be suitable to treat pediatric patients 0-12 months old as well as adult patients with obstructive hydrocephalus who fail traditional shunts or are eligible for endoscopy. Current progress, including platform optimization, Bionaut™ control, and real-time imaging and in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of ovine models, will be discussed.

Keywords: Bionaut™, cerebrospinal fluid, CSF, fenestration, hydrocephalus, micro-robot, microsurgery

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Authors: Azza A. Ali, Abeer I. Abd El-Fattah, Shaimaa S. Hussein, Hanan A. Abd El-Samea, Karema Abu-Elfotuh

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Background: Aluminium (Al) represents an environmental risk factor. Exposure to high levels of Al causes neurotoxic effects and different diseases. Vinpocetine is widely used to improve cognitive functions, it possesses memory-protective and memory-enhancing properties and has the ability to increase cerebral blood flow and glucose uptake. Cocoa bean represents a rich source of iron as well as a potent antioxidant. It can protect from the impact of free radicals, reduces stress as well as depression and promotes better memory and concentration. Wheatgrass is primarily used as a concentrated source of nutrients. It contains vitamins, minerals, carbohydrates, amino acids and possesses antioxidant and anti-inflammatory activities. Coenzyme Q10 (CoQ10) is an intracellular antioxidant and mitochondrial membrane stabilizer. It is effective in improving cognitive disorders and has been used as anti-aging. Zinc is a structural element of many proteins and signaling messenger that is released by neural activity at many central excitatory synapses. Objective: To study the role of some nutrients and drugs as Vinpocetine, Cocoa, Wheatgrass, CoQ10 and Zinc against neurotoxicity induced by Al in rats as well as to compare between their potency in providing protection. Methods: Seven groups of rats were used and received daily for three weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except for the control group which received saline. All groups of Al-toxicity model except one group (non-treated) were co-administered orally together with AlCl3 the following treatments; Vinpocetine (20mg/kg), Cocoa powder (24mg/kg), Wheat grass (100mg/kg), CoQ10 (200mg/kg) or Zinc (32mg/kg). Biochemical changes in the rat brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups besides histopathological examinations in different brain regions. Results: Neurotoxicity and neurodegenerations in the rat brain after three weeks of Al exposure were indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the significant decrease in SOD, TAC, BDNF and confirmed by the histopathological changes in the brain. On the other hand, co-administration of each of Vinpocetine, Cocoa, Wheatgrass, CoQ10 or Zinc together with AlCl3 provided protection against hazards of neurotoxicity and neurodegenerations induced by Al, their protection were indicated by the decrease in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the increase in SOD, TAC, BDNF and confirmed by the histopathological examinations of different brain regions. Vinpocetine and Cocoa showed the most pronounced protection while Zinc provided the least protective effects than the other used nutrients and drugs. Conclusion: Different degrees of protection from neurotoxicity and neuronal degenerations induced by Al could be achieved through the co-administration of some nutrients and drugs during its exposure. Vinpocetine and Cocoa provided the most protection than Wheat grass, CoQ10 or Zinc which showed the least protective effects.

Keywords: aluminum, neurotoxicity, vinpocetine, cocoa, wheat grass, coenzyme Q10, Zinc, rats

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Authors: Su Yin Chiam, Zhipeng Ding, Guang Yang, Danny Jian Hang Tng, Peiyi Song, Geok Ing Ng, Ken-Tye Yong, Qing Xin Zhang

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Brain-machine interfaces (BMI) is a ground rich of exploration opportunities where manipulation of neural activity are used for interconnect with myriad form of external devices. These research and intensive development were evolved into various areas from medical field, gaming and entertainment industry till safety and security field. The technology were extended for neurological disorders therapy such as obsessive compulsive disorder and Parkinson’s disease by introducing current pulses to specific region of the brain. Nonetheless, the work to develop a real-time observing, recording and altering of neural signal brain-machine interfaces system will require a significant amount of effort to overcome the obstacles in improving this system without delay in response. To date, feature size of interface devices and the density of the electrode population remain as a limitation in achieving seamless performance on BMI. Currently, the size of the BMI devices is ranging from 10 to 100 microns in terms of electrodes’ diameters. Henceforth, to accommodate the single cell level precise monitoring, smaller and denser Nano-scaled nanowire electrode arrays are vital in fabrication. In this paper, we would like to showcase the fabrication of high aspect ratio of vertical silicon nanowire electrodes arrays using microelectromechanical system (MEMS) method. Nanofabrication of the nanowire electrodes involves in deep reactive ion etching, thermal oxide thinning, electron-beam lithography patterning, sputtering of metal targets and bottom anti-reflection coating (BARC) etch. Metallization on the nanowire electrode tip is a prominent process to optimize the nanowire electrical conductivity and this step remains a challenge during fabrication. Metal electrodes were lithographically defined and yet these metal contacts outline a size scale that is larger than nanometer-scale building blocks hence further limiting potential advantages. Therefore, we present an integrated contact solution that overcomes this size constraint through self-aligned Nickel silicidation process on the tip of vertical silicon nanowire electrodes. A 4 x 4 array of vertical silicon nanowires electrodes with the diameter of 290nm and height of 3µm has been successfully fabricated.

Keywords: brain-machine interfaces, microelectromechanical systems (MEMS), nanowire, nickel silicide

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Authors: Muhammad Badruzzaman, Alif Hasan, Md. Shahjahan

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Propiconazole is a triazole fungicide extensively used in agriculture which can harm to non-target organisms in aquatic environment through runoff. Chronic exposure to environmental pesticides turn to behavioral impairment in vertebrates including teleosts. However, the potential effect of this fungicide on neurobehavioral impairment and release from it in vertebrates has not been fully explored. In this work, we examined the role of melatonin to rescue fungicide induced neurobehavioral and reproductive alternation and its connection with changes in dopaminergic activity in the brain of Mystus cavasius. After fish were exposed to water containing propiconazole at 0, 0.1, 5, and 250 µg/L for 3 days, significant increases of DA, 3,4-dihydroxyphenylacetic acid (DOPAC; a DA metabolite), and their ratio (DOPAC/DA) were observed in whole brain at 250 µg/L concentration. When fish were treated with propiconazole at 250 µg/L for 3 days, there was a significant elevation of DA, DOPAC and DOPAC/DA in diencephalon and pituitary, and only DA in the telencephalon, compared with control fish. Besides, it induced a reduction in extracellular serotonin and had an anxiolytic-like effect, supported by a decrease in cortisol production. Increased locomotor activity, anxiety and aggressiveness, decreased gonadosomatic index with few vitellogenic oocytes in ovaries after propiconazole treatment. When fish were treated with melatonin, D1 (SCH-23390) or D2 (Haloperidol) dopamine receptor antagonists and combined of melatonin and D1/D2 receptor antagonist and was observed melatonin + D2 receptor antagonist rescued fungicide induced all behavioral changes in fish. These results indicate that propiconazole increases locomotor activity, anxiety and aggressiveness and decreases reproductive activity, which was rescued by combined treatment of melatonin and dopamine receptor antagonist.

Keywords: behavior, catfish, dopamine, fungicide, melatonin

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Authors: P. Donnelly, G. Mitchell

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Traumatic Brain Injury (TBI) is a major contributor to the global burden of disease; despite its ubiquity, there is significant variation in diagnosis, prognosis, and treatment between clinicians. This study aims to examine the spectrum of approaches that currently exist at a Level 1 Trauma Centre in Australasia by surveying Emergency Physicians and Neurosurgeons on those aspects of mTBI. A pilot survey of 17 clinicians (Neurosurgeons, Emergency Physicians, and others who manage patients with mTBI) at a Level 1 Trauma Centre in Brisbane, Australia, was conducted. The objective of this study was to examine the importance these clinicians place on various elements in their approach to the diagnosis, prognostication, and treatment of mTBI. The data were summarised, and the descriptive statistics reported. Loss of consciousness and post-traumatic amnesia were rated as the most important signs or symptoms in diagnosing mTBI (median importance of 8). MRI was the most important imaging modality in diagnosing mTBI (median importance of 7). ‘Number of the Previous TBIs’ and Intracranial Injury on Imaging’ were rated as the most important elements for prognostication (median importance of 9). Education and reassurance were rated as the most important modality for treating mTBI (median importance of 7). There was a statistically insignificant variation between the specialties as to the importance they place on each of these components. In this Australian tertiary trauma center, there appears to be variation in how clinicians approach mTBI. This study is underpowered to state whether this is between clinicians within a specialty or a trend between specialties. This variation is worthwhile in investigating as a step toward a unified approach to diagnosing, prognosticating, and treating this common pathology.

Keywords: mild traumatic brain injury, adult, clinician, survey

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Authors: John Gaber, Youssef Ahmed, Hossam A.Gabbar, Jing Ren

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Nuclear Power Plant (NPP) operators have a large responsibility on their shoulders. They must allow the plant to generate a high amount of energy while inspecting and maintaining the safety of the plant. This type of occupation comes with high amounts of mental fatigue, and a small mistake can have grave consequences. Electroencephalography (EEG) is a method of gathering the electromagnetic waves emitted by a human brain. We propose a safety system by monitoring brainwaves for signs of mental fatigue. This requires an analysis of the tasks and mental models of the NPP operator, as well as risk factors on mental fatigue and attention that NPP operators face when performing their tasks. The brain waves generated from experiencing mental fatigue can then be monitored for. These factors are analyzed, developing an EEG-based monitoring system, which aims to alert NPP operators when levels of mental fatigue and attention start affecting their performance in task completion.

Keywords: EEG, power plant operator, psychology, task analysis

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Authors: Kgopa Bontle, Tholen Sodi

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Climate change poses a major threat to the well-being of both people and the environment, with subsistence farmers most affected as they rely on local supply systems that are sensitive to climate variation. This study documented psychological resilience factors associated with climate change adaptations by subsistence farmers in Maruleng Municipality, Limpopo Province. A qualitative study was conducted to examine the notions of climate change by subsistence farmers, the psychological resilience factors, the strategies to cope with climate change, adaptation methods, and the development of subsistence farmers’ psychological resilience factors model. Data were collected through direct interactions with participants using a grounded theory research design. An open-ended interview was used to collect data with a sample of 15 participants selected through theoretical sampling in Maruleng Municipality. The participants were both Sepedi and Xitsonga speaking from 2 villages, mostly unemployed, pensioners and dependent on social grants. The study included both males and females who were predominately the elderly. The research findings indicate that farmers have limited knowledge of what climate change is and what causes it. Furthermore, the research reflects that although their responses were non-scientific but sensible enough to know what they were dealing with. They mentioned extreme weather, which includes hot days and less rainfall and changes in seasons, as some of the impacts brought by climate change. The results also indicated that participants have learned to adapt through several adaptation strategies, including mulching, changes in irrigation time slots and being innovative. The resilience factors that emerged from the study were a passion for farming, hope, enthusiasm, courage, acceptance/tolerance, livelihood and belief systems. Looking at the socio-economic factors of the current study setting argumentation leads to the conclusion that it is important that government should assist the subsistence farmers as it was observed from the participants that they felt neglected by the government and policymakers as they are small scale farmers and are not included like commercial farmers.

Keywords: climate change, psychological resilience factors, human adaptation, subsistence farmers

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Authors: Tanveer Ahmed Choudhury

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Background: Bangladesh is one of the largest deltas in the world, with high population density and high rates of poverty and illiteracy. 80% of the country is on low-lying floodplains, leaving the country one of the most vulnerable to the adverse effects of climate change: sea level rise, cyclones and storms, salinity intrusion, rising temperatures and heavy monsoon downpours. Such climatic events already limit Economic Development in the country. Although Bangladesh has had little responsibility in contributing to global climatic change, it is vulnerable to both its direct and indirect impacts. Real threats include reduced agricultural production, worsening food security, increased incidence of flooding and drought, spreading disease and an increased risk of conflict over scarce land and water resources. Currently, 8.3 million Bangladeshis live in cyclone high risk areas. However, by 2050 this is expected to grow to 20.3 million people, if proper adaptive actions are not taken. Under a high emissions scenario, an additional 7.6 million people will be exposed to very high salinity by 2050 compared to current levels. It is also projected that, an average of 7.2 million people will be affected by flooding due to sea level rise every year between 2070-2100 and If global emissions decrease rapidly and adaptation interventions are taken, the population affected by flooding could be limited to only about 14,000 people. To combat the climate change adverse effects, Bangladesh government has initiated many adaptive measures specially in infrastructure and renewable energy sector. Government is investing huge money and initiated many projects which have been proved very success full. Objectives: The objective of this paper is to describe some successful measures initiated by Bangladesh government in its effort to make the country a Climate Resilient. Methodology: Review of operation plan and activities of different relevant Ministries of Bangladesh government. Result: The following initiative projects, programs and activities are considered as best practices for Climate Change adaptation successes for Bangladesh: 1. The Infrastructure Development Company Limited (IDCOL); 2. Climate Change and Health Promotion Unit (CCHPU); 3. The Climate Change Trust Fund (CCTF); 4. Community Climate Change Project (CCCP); 5. Health, Population, Nutrition Sector Development Program (HPNSDP, 2011-2016)- "Climate Change and Environmental Issues"; 6. Ministry of Health and Family Welfare, Bangladesh and WHO Collaboration; - National Adaptation Plan. -"Building adaptation to climate change in health in least developed countries through resilient WASH". 7. COP-21 “Climate and health country profile -2015 Bangladesh. Conclusion: Due to a vast coastline, low-lying land and abundance of rivers, Bangladesh is highly vulnerable to climate change. Having extensive experience with facing natural disasters, Bangladesh has developed a successful adaptation program, which led to a significant reduction in casualties from extreme weather events. In a low income country setting, Bangladesh had successfully adapted various projects and initiatives to combat future Climate Change challenges.

Keywords: climate, change, success, Bangladesh

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Authors: Jagmeet S. Kanwal, Julia F. Langley

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Music can heal the body, but a mechanistic understanding of this phenomenon is lacking. This study explores the effects of music presentation on neurologic and physiologic responses leading to metabolic changes in the human body. The mind and body co-exist in a corporeal entity and within this framework, sickness ensues when the mind-body balance goes awry. It is further hypothesized that music has the capacity to directly reset this balance. Two lines of inquiry taken together can provide a mechanistic understanding of this phenomenon 1) Empirical evidence for a sound-sensitive pressure sensor system in the body, and 2) The notion of a “healing center” within the brain that is activated by specific patterns of sounds. From an acoustics perspective, music is spatially distributed as pressure waves ranging from a few cm to several meters in wavelength. These waves interact and propagate in three-dimensions in unique ways, depending on the wavelength. Furthermore, music creates dynamically changing wave-fronts. Frequencies between 200 Hz and 1 kHz generate wavelengths that range from 5'6" to 1 foot. These dimensions are in the range of the body size of most people making it plausible that these pressure waves can geometrically interact with the body surface and create distinct patterns of pressure stimulation across the skin surface. For humans, short wavelength, high frequency (> 200 Hz) sounds are best received via cochlear receptors. For low frequency (< 200 Hz), long wavelength sound vibrations, however, the whole body may act as an ideal receiver. A vast array of highly sensitive pressure receptors (Pacinian corpuscles) is present just beneath the skin surface, as well as in the tendons, bones, several organs in the abdomen, and the sexual organs. Per the available empirical evidence, these receptors contribute to music perception by allowing the whole body to function as a sound receiver, and knowledge of how they function is essential to fully understanding the therapeutic effect of music. Neuroscientific studies have established that music stimulates the limbic system that can trigger states of anxiety, arousal, fear, and other emotions. These emotional states of brain activity play a crucial role in filtering top-down feedback from thoughts and bottom-up sensory inputs to the autonomic system, which automatically regulates bodily functions. Music likely exerts its pleasurable and healing effects by enhancing functional and effective connectivity and feedback mechanisms between brain regions that mediate reward, autonomic, and cognitive processing. Stimulation of pressure receptors under the skin by low-frequency music-induced sensations can activate multiple centers in the brain, including the amygdala, the cingulate cortex, and nucleus accumbens. Melodies in music in the low (< 600 Hz) frequency range may augment auditory inputs after convergence of the pressure-sensitive inputs from the vagus nerve onto emotive processing regions within the limbic system. The integration of music-generated auditory and somato-visceral inputs may lead to a synergistic input to the brain that promotes healing. Thus, music can literally heal humans through “touch” as it energizes the brain’s autonomic system for restoring homeostasis.

Keywords: acoustics, brain, music healing, pressure receptors

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Authors: Parvin Goli, Amirhosein Kefayat, Rezvan Goli

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Background: It is well established that parents can influence their offspring's neurodevelopment. It is shown that paternal environment and lifestyle is beneficial for the progeny's fitness and might affect their metabolic mechanisms; however, the effects of paternal exercise on the brain in the offspring have not been explored in detail. Objective: This study aims to review the impact of paternal physical exercise on memory and learning, neuroplasticity, as well as DNA methylation levels in the off-spring's hippocampus. Study design: In this systematic review and meta-analysis, an electronic literature search was conducted in databases including PubMed, Scopus, and Web of Science. Eligible studies were those with an experimental design, including an exercise intervention arm, with the assessment of any type of memory function, learning ability, or any type of brain plasticity as the outcome measures. Standardized mean difference (SMD) and 95% confidence intervals (CI) were computed as effect size. Results: The systematic review revealed the important role of environmental enrichment in the behavioral development of the next generation. Also, offspring of exercised fathers displayed higher levels of memory ability and lower level of brain-derived neurotrophic factor. A significant effect of paternal exercise on the hippocampal volume was also reported in the few available studies. Conclusion: These results suggest an intergenerational effect of paternal physical activity on cognitive benefit, which may be associated with hippocampal epigenetic programming in offspring. However, the biological mechanisms of this modulation remain to be determined.

Keywords: hippocampal plasticity, learning ability, memory, parental exercise

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Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.

Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones

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Authors: Claudio Burguez, María Castelló, Mikaela Pisani, Marcos Umpiérrez

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BIOFEEDBACK exhibition offers a unique experience for each visitor, combining art, neuroscience, and technology in an interactive way. Using a headband that captures the bioelectric activity of the brain, the visitors are able to generate sound and images in a sequence loop, making them an integral part of the artwork. Through this interactive exhibit, visitors gain a deeper appreciation of the beauty and complexity of the brain. As a special takeaway, visitors will receive an NFT as a present, allowing them to continue their engagement with the exhibition beyond the physical space. We used the EEG Biofeedback technique following a closed-loop neuroscience approach, transforming EEG data captured by a Muse S headband in real-time into audiovisual stimulation. PureData is used for sound generation and Generative Adversarial Networks (GANs) for image generation. Thirty participants have experienced the exhibition. For some individuals, it was easier to focus than others. Participants who said they could focus during the exhibit stated that at one point, they felt that they could control the sound, while images were more abstract, and they did not feel that they were able to control them.

Keywords: art, audiovisual, biofeedback, EEG, NFT, neuroscience, technology

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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