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1.
BMC Med Educ ; 17(1): 225, 2017 Nov 21.
Article in English | MEDLINE | ID: mdl-29162061

ABSTRACT

BACKGROUND: With an aging American population, the burden of neurologic disease is intensifying and the decline in neurology residents and practicing neurologists is leaving these patients helpless and unable to find care. 'Neurophobia', a chronic illness that begins early in medical school, has been identified as a cause for the low number of neurology residents. METHODS: A longitudinal study surveyed medical students at the beginning of their first year (M1) and then again at the beginning of their second year (M2). Three neuroscience educational interventions were studied: team based learning (TBL), case based teaching (CBT), and problem based learning (PBL). Participants provided self-reported neurophobia levels, attitudes about neuroscience, and the effectiveness of educational interventions. RESULTS: A total of 446 students during M1 and 206 students during M2 participated in the survey. A significant change in self-reported neurophobia (p = 0.035) was observed from 19% in M1 to 26% in M2. Neuroscience knowledge and confidence managing a neurologic condition also significantly increased (p < 0.001 and p = 0.038 respectively). Perceived interest, difficulty, and desire to pursue a career in neuroscience did not a change significantly. Majority of students perceived CBT (76%), TBL (56%), and PBL (66%) beneficial. Only CBT demonstrated a statistical difference (p = 0.026) when stratified by self-reported change in neurophobia. CONCLUSION: An increase in neurophobia after completing a neuroscience was observed but the prevalence rate of 26% was lower than previous studies. Knowledge about neuroscience increased significantly and educational interventions were considered beneficial by students. Thus, interventions that increase knowledge and decrease neurophobia can lead to an increase in students pursuing neurology residencies.


Subject(s)
Attitude of Health Personnel , Career Choice , Neurology/education , Neurosciences/education , Students, Medical/psychology , Adult , Education, Medical, Undergraduate/methods , Female , Grenada , Humans , Longitudinal Studies , Male , Phobic Disorders , Problem-Based Learning , Self Report , Statistics, Nonparametric , Young Adult
2.
Epilepsy Behav ; 70(Pt A): 232-237, 2017 05.
Article in English | MEDLINE | ID: mdl-28448942

ABSTRACT

Epilepsy is a chronic neurological disorder that is increasingly prevalent in developing countries. It is critical to provide appropriate support to patients during seizures in order to prevent injuries. False beliefs regarding the etiology or pathogenesis of the epilepsy and inadequate health information may put patients with epilepsy or other seizure disorders at increased risk of injury. Our objective was to assess the level of epilepsy awareness amongst the general population in Grenada and educate the participants regarding proper first-aid measures. A pilot questionnaire containing a total of 25 items surveying the knowledge, attitudes, and first-aid care of epilepsy was presented to 200 adult residents of Grenada as face-to-face interviews. Study participants were recruited over a nine-month period on a voluntary basis at health fairs, in local communities, and on the campus of St. George's University. Our results indicate that 35 out of 198 (17.7%) respondents erroneously believed that medicine should be placed in a person's mouth during a seizure, and 83 out of 200 (41.5%) answered that a person who is convulsing should be held down. Furthermore, 128 out of 195 (65.6%) respondents erroneously believed that seizures occur when there is low brain activity and an additional 35 out of 199 (17.6%) regarded epilepsy as a contagious disorder. Our data suggest that persons with seizures and/or epilepsy may be at increased risk of injury in Grenada due to common misconceptions and false beliefs. It is critical that epilepsy awareness is promoted in developing countries, such as Grenada, where inadequate health information may be common.


Subject(s)
Developing Countries , Epilepsy/epidemiology , Epilepsy/therapy , First Aid/methods , Health Knowledge, Attitudes, Practice , Surveys and Questionnaires , Adolescent , Adult , Aged , Awareness , Epilepsy/diagnosis , Female , Grenada , Humans , Male , Middle Aged , Pilot Projects , Random Allocation , Seizures , Young Adult
3.
Neurochem Res ; 41(4): 731-47, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26518675

ABSTRACT

Human SH-SY5Y neuroblastoma cells maintain their potential for differentiation and regression in culture conditions. The induction of differentiation could serve as a strategy to inhibit cell proliferation and tumor growth. Previous studies have shown that differentiation of SH-SY5Y cells can be induced by all-trans-retinoic-acid (RA) and cholesterol (CHOL). However, signaling pathways that lead to terminal differentiation of SH-SY5Y cells are still largely unknown. The goal of this study was to examine in the RA and CHOL treated SH-SY5Y cells the additive impacts of estradiol (E2) and brain-derived neurotrophic factor (BDNF) on cell morphology, cell population growth, synaptic vesicle recycling and presence of neurofilaments. The above features indicate a higher level of neuronal differentiation. Our data show that treatment for 10 days in vitro (DIV) with RA alone or when combined with E2 (RE) or CHOL (RC), but not when combined with BDNF (RB), significantly (p < 0.01) inhibited the cell population growth. Synaptic vesicle recycling, induced by high-K(+) depolarization, was significantly increased in all treatments where RA was included (RE, RC, RB, RCB), and when all agents were added together (RCBE). Specifically, our results show for the first time that E2 treatment can alone increase synaptic vesicle recycling in SH-SY5Y cells. This work contributes to the understanding of the ways to improve suppression of neuroblastoma cells' population growth by inducing maturation and differentiation.


Subject(s)
Cholesterol/pharmacology , Estradiol/pharmacology , Neurons/drug effects , Tretinoin/pharmacology , Brain-Derived Neurotrophic Factor/pharmacology , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Humans , Intermediate Filaments/drug effects , Intermediate Filaments/ultrastructure , Neuroblastoma , Neurons/cytology , Synaptic Vesicles/drug effects , Synaptic Vesicles/ultrastructure
5.
Epilepsy Behav ; 51: 267-72, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26312988

ABSTRACT

Very little has been reported about the health resources available for patients with epilepsy in the five English-speaking southern Caribbean countries of Trinidad and Tobago, Barbados, Grenada, Saint Vincent and the Grenadines, and Saint Lucia. There is no comprehensive resource describing their health systems, access to specialty care, antiepileptic drug (AED) use, and availability of brain imaging and EEG. The purpose of this study was to profile epilepsy care in these countries as an initial step toward improving the standard of care and identifying gaps in care to guide future policy changes. In each southern Caribbean country, we conducted study visits and interviewed health-care providers, government health ministers, pharmacy directors, hospital medical directors, pharmacists, clinic staff, radiologists, and radiology and EEG technicians. Health-care providers completed extensive epilepsy care surveys. The five countries all have integrated government health systems with clinics and hospitals that provide free or heavily subsidized care and AEDs for patients with epilepsy. Only Trinidad and Tobago and Barbados, however, have neurology specialists. The three smaller countries lack government imaging and EEG facilities. Trinidad had up to one-year waits for public MRI/EEG. Government formularies in Grenada, Saint Vincent and the Grenadines, and Saint Lucia are limited to first-generation AEDs. One or more second-line agents are formulary in Trinidad and Barbados. Nonformulary drugs may be obtained for individual patients in Barbados. Grenada, Saint Lucia, and Saint Vincent and the Grenadines participate in an Organization of Eastern Caribbean States formulary purchasing system, which added levetiracetam following the survey. Newer generic AED formulations with the lowest risks for pregnancy malformation were not in use. In conclusion, patients with epilepsy in the southern Caribbean have excellent access to government clinics and hospitals, but AED choices are limited. Local medical providers reported that the major limitations in care were lack of specialty care, lack of imaging and EEG services, financial barriers to care, long wait times for care, and limited access to additional AEDs.


Subject(s)
Delivery of Health Care/statistics & numerical data , Epilepsy/epidemiology , Epilepsy/therapy , Anticonvulsants/supply & distribution , Barbados , Caribbean Region/epidemiology , Developing Countries , Drug Utilization , Electroencephalography , Female , Formularies as Topic , Health Personnel/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Humans , Male , Neurology/statistics & numerical data , Pregnancy , Saint Lucia , Saint Vincent and the Grenadines
6.
Curr Alzheimer Res ; 12(5): 445-61, 2015.
Article in English | MEDLINE | ID: mdl-25938871

ABSTRACT

Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aß), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid/metabolism , Animals , Humans , Protein Folding
7.
Prog Mol Biol Transl Sci ; 123: 191-217, 2014.
Article in English | MEDLINE | ID: mdl-24560146

ABSTRACT

In this chapter, we review the principal astrocyte functions and the interactions between neurons and astrocytes. We then address how the experimentally observed functions have been verified in computational models and review recent experimental literature on astrocyte-neuron interactions. Benefits of computational neuroscience work are highlighted through selected studies with neurons and astrocytes by analyzing the existing models qualitatively and assessing the relevance of these models to experimental data. Common strategies to mathematical modeling and computer simulation in neuroscience are summarized for the nontechnical reader. The astrocyte-neuron interactions are then further illustrated by examples of some neurological and neurodegenerative diseases, where the miscommunication between glia and neurons is found to be increasingly important.


Subject(s)
Astrocytes/cytology , Cell Communication , Models, Neurological , Neurons/cytology , Translational Research, Biomedical , Animals , Computer Simulation , Humans
8.
PLoS One ; 6(3): e17914, 2011 Mar 29.
Article in English | MEDLINE | ID: mdl-21483471

ABSTRACT

BACKGROUND: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer's disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer's disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25-35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25-35. A25-35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25-35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. CONCLUSIONS/SIGNIFICANCE: Nanomolar A25-35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25-35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system.


Subject(s)
Astrocytes/drug effects , Astrocytes/metabolism , Fura-2/analogs & derivatives , Glutamic Acid/pharmacology , Models, Theoretical , Serotonin/pharmacology , Animals , Calcium Signaling/drug effects , Cells, Cultured , Fura-2/chemistry , Rats , Rats, Sprague-Dawley
9.
Biochem Biophys Res Commun ; 379(2): 562-6, 2009 Feb 06.
Article in English | MEDLINE | ID: mdl-19118523

ABSTRACT

In this study canine parvovirus, CPV, was found to induce disorder in DPPC:cholesterol membranes in acidic conditions. This acidicity-induced fluidizing effect is suggested to originate from the N-terminus of the viral capsid protein VP1. In accordance with the model membrane studies, a fluidizing effect was seen also in the endosomal membranes during CPV infection implying an important functional role of the fluidization in the endocytic entry of the virus.


Subject(s)
Capsid Proteins/chemistry , Capsid/chemistry , Cholesterol/chemistry , Membrane Fluidity , Membranes, Artificial , Parvovirus, Canine/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Hydrogen-Ion Concentration
10.
J Neurochem ; 102(6): 1941-1952, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17540009

ABSTRACT

Synaptic vesicle formation, vesicle activation and exo/endocytosis in the pre-synaptic area are central steps in neuronal communication. The formation and localization of synaptic vesicles in human SH-SY5Y neuroblastoma cells, differentiated with 12-o-tetradecanoyl-phorbol-13-acetate, dibutyryl cyclic AMP, all-trans-retinoic acid (RA) and cholesterol, was studied by fluorescence microscopy and immunocytochemical methods. RA alone or together with cholesterol, produced significant neurite extension and formation of cell-to-cell contacts. Synaptic vesicle formation was followed by anti-synaptophysin (SypI) and AM1-43 staining. SypI was only weakly detected, mainly in cell somata, before 7 days in vitro, after which it was found in neurites. Depolarization of the differentiated cells with high potassium solution increased the number of fluorescent puncta, as well as SypI and AM1-43 co-localization. In addition to increase in the number of synaptic vesicles, RA and cholesterol also increased the number and distribution of lysosome-associated membrane protein 2 labeled lysosomes. RA-induced Golgi apparatus fragmentation was partly avoided by co-treatment with cholesterol. The SH-SY5Y neuroblastoma cell line, differentiated by RA and cholesterol and with good viability in culture, is a valuable tool for basic studies of neuronal metabolism, specifically as a model for dopaminergic neurons.


Subject(s)
Cell Differentiation/drug effects , Cholesterol/pharmacology , Presynaptic Terminals/drug effects , Synaptic Vesicles/drug effects , Tretinoin/pharmacology , Cell Differentiation/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Cholesterol/metabolism , Dopamine/metabolism , Drug Synergism , Growth Cones/drug effects , Growth Cones/metabolism , Humans , Lysosomal-Associated Membrane Protein 2/drug effects , Lysosomal-Associated Membrane Protein 2/metabolism , Microscopy, Fluorescence , Models, Biological , Neurites/drug effects , Neurites/metabolism , Neuroblastoma , Potassium/pharmacology , Presynaptic Terminals/metabolism , Pyridinium Compounds , Quaternary Ammonium Compounds , Synapses/drug effects , Synapses/metabolism , Synaptic Vesicles/metabolism , Synaptophysin/metabolism , Tretinoin/metabolism
11.
Neurosci Lett ; 396(2): 102-7, 2006 Mar 27.
Article in English | MEDLINE | ID: mdl-16356645

ABSTRACT

A new automated image analysis method for quantification of fluorescent dots is presented. This method facilitates counting the number of fluorescent puncta in specific locations of individual cells and also enables estimation of the number of cells by detecting the labeled nuclei. The method is here used for counting the AM1-43 labeled fluorescent puncta in human SH-SY5Y neuroblastoma cells induced to differentiate with all-trans retinoic acid (RA), and further stimulated with high potassium (K+) containing solution. The automated quantification results correlate well with the results obtained manually through visual inspection. The manual method has the disadvantage of being slow, labor-intensive, and subjective, and the results may not be reproducible even in the intra-observer case. The automated method, however, has the advantage of allowing fast quantification with explicitly defined methods, with no user intervention. This ensures objectivity of the quantification. In addition to the number of fluorescent dots, further development of the method allows its use for quantification of several other parameters, such as intensity, size, and shape of the puncta, that are difficult to quantify manually.


Subject(s)
Artificial Intelligence , Cell Transformation, Neoplastic/pathology , Image Interpretation, Computer-Assisted/methods , Microscopy, Fluorescence/methods , Neuroblastoma/pathology , Pattern Recognition, Automated/methods , Transport Vesicles/pathology , Algorithms , Cell Differentiation , Cell Line, Tumor , Fuzzy Logic , Humans , Reproducibility of Results , Sensitivity and Specificity
12.
J Neurol ; 249(5): 576-83, 2002 May.
Article in English | MEDLINE | ID: mdl-12021948

ABSTRACT

Chemokines are small chemoattractant cytokines which participate in the migration of immune cells into the CNS and contribute to the T cell-mediated pathogenesis of multiple sclerosis (MS). The expression of chemokines and their receptors in freshly isolated mononuclear cells from peripheral blood (PBMC) was studied in relation to MS subtype, disease duration and progression in a total of 57 patients with MS (22 relapsing remitting, RRMS; 21 secondary progressive, SPMS; 14 primary progressive, PPMS) and 17 healthy controls. The RNA expression of CCR5 in PBMC was analysed by reverse transcription polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. The PBMC levels of CCR5-ligands MIP-1 alpha/beta and RANTES, and chemokines MCP-1, IL-8, lymphotactin, IP-10 and I-309 were analysed by ribonuclease protection assay (RPA). Significantly increased intracellular CCR5 RNA expression intensity was detected in PPMS when compared with SPMS ( p=0.009), RRMS ( p=0.013), and controls ( p=0.023). However, the surface expression of CCR5 on CD4(+) cells from PBMC, analysed by flow cytometry, appeared to be similar in all MS subtypes and controls. The CCR5-ligands RANTES and MIP-1b were expressed constitutively in all patients and controls. Interleukin-8 was found in all MS subtypes and controls, but IP-10 was detected only in RRMS and SPMS, and lymphotactin occasionally in other subtypes but PPMS. MCP-1, MIP-1a or I-309 were not expressed in any of the groups studied. A correlation was found between the RNA levels of RANTES and CCR5 in PPMS ( r=0.735). Differential profile in the expression of CCR5 and chemokines between PPMS and other MS subtypes may contribute to differences in the pathogenesis of MS and thus can be of importance in the development of new treatments for MS.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Chemokines/metabolism , Chemotaxis, Leukocyte/immunology , Multiple Sclerosis/blood , Receptors, CCR5/genetics , Adult , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , Chemokine CCL1 , Chemokine CCL2/metabolism , Chemokine CCL4 , Chemokine CCL5/metabolism , Chemokines, CC/metabolism , Flow Cytometry , Gene Expression Regulation/immunology , Humans , Interleukin-8/metabolism , Intracellular Fluid/immunology , Intracellular Fluid/metabolism , Macrophage Inflammatory Proteins/metabolism , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/immunology , RNA, Messenger/metabolism , Receptors, Chemokine/metabolism
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