Esta pesquisa aborda, a partir de uma perspectiva bioarqueológica comparativa, a problemática das mudanças nos padrões de subsistência associados à intensificação da agricultura e suas implicações no processo de complexificação social na costa dos Andes Centrais. Para tanto, se examinaram indicadores de patologia oral, estresse nutricional e isótopos estáveis, e outros dados paleodietéticos e arqueológicos de 09 populações pré-históricas da costa dos Andes Centrais datadas para o período Formativo (~3000-1 a.C.). Os resultados mostram que as dietas a predomínio de carboidratos são muito antigas na região, inclusive nos sítios litorâneos e que o processo de complexificação ocorreu em presença da agricultura como base econômica. As formações teocráticas do 3ro e 2do milênios a.C. floresceram baseadas na agricultura de tubérculos, leguminosas, árvores frutíferas e milho em menor quantidade (abaixo de 20%), apelando a técnicas agrícolas adaptadas às características de aridez dos vales da bacia do Pacífico. Uma drástica mudança na dieta costeira andina ocorreu entre 500-1 a.C., quando o milho passa ser o principal produto de subsistência ao nível regional em concomitância com o aparecimento de governos seculares. / From a comparative bioarchaeological perspective this research addresses the issue of changes in subsistence patterns associated with the intensification of agriculture on the coast of the Central Andes and their implications to the social complexity process. Markers of oral pathology and nutritional stress were examined, along with stable isotopes, and other paleodietetic and archaeological data of 09 prehistoric coastal populations dated to the Formative period (~3000-1 BC). The results show that the predominance of rich carbohydrate diets is very old in the region, also on shoreline settlements, and the process of complexity was based in agriculture as an economic basis. The theocratic societies of 3rd and 2nd millennium BC flourished based on agriculture of tubers, legumes, fruit trees and corn in smaller quantities (below 20%), using farming techniques highly adapted to the aridity of the Pacific basin valleys. A drastic change in the Andean coastal diet occurred between 500-1 BC, when the corn became the main regional staple concomitant to the appearance of secular governments

RESUMO Os índices de prevalência das anomalias dentárias, sua distribuição por sexo, idade, arcada e lado têm variado de um autor para outro, e também, de acordo com a população pesquisada. Esta pesquisa foi desenvolvida no município de Belém, onde foram avaliadas 500 radiografias panorâmicas, de crianças de ambos os sexos, com a finalidade de se identificar a ocorrência das seguintes anomalias : Anodontia, Taurodontia, Dentes não irrompidos, Microdontia, Macrodontia, Dentes supranumerários e Geminação. Foi objetivo desta pesquisa, a partir das radiografias analisadas, buscar a caracterização das crianças avaliadas, possibilitando o diagnóstico, o mais precoce possível, facilitando as soluções terapêuticas. A análise dos resultados aferidos permite inferir que a amostra pesquisada apresenta traços característicos. Foram analisadas 500 radiografias panorâmicas, de 240 crianças do sexo masculino e 260 crianças do sexo feminino, sendo encontrados 118 casos de anomalias, perfazendo um prevalência de 16%.De acordo com as anomalias pesquisadas encontrou - se as seguintes prevalências: Anodontia (5,4%), Taurodontia (1,0%), Dentes não irrompidos (4,2%), Microdontia (2,0%), Macrodontia (0,6%), Dentes supranumerários (2,4%) e Geminação (0,4%). / SUMMARY The rates of Dental prevalence of anomalies, its distribution per sex, age, arcade e side varies from author to author, and also according to the researched population. For this research was developed in the city of Belém where, 500 panoramic radiographies of children of both sexes were inspected in order to identify the happening of the following anomalies : Anodontia, Taurodontia, Unbroken out teeth, Microdontia, Macrodontia,Supernumerary teeth, Gemination. The purpose of this research, after the study of the radiographies, was to develop the haracterization of the appraised children in order to determine the therapeutic solutions.The analysis of the gauged results allows the conclusion that the researched sample presents characteristic features.There were found 118 cases of anomalies, completing a prevalence of 16%. According to the anomalies researched there were found the following prevalence rates : Anodontia ( 5,4% ), Taurodontia ( 1,0% ), Unbroken out teeth ( 4,2% ), Microdontia ( 2,0% ), Macrodontia ( 0,6% ) and Gemination ( 0,4% ).

Candida albicans is an opportunistic pathogen that is present in the normal flora in a majority of individuals. One key factor in C. albicans virulence is the ability to change its morphology from yeast to an elongated or hyphal form. The regulation of this morphogenesis relies in part upon quorum sensing (QS) molecules. C. albicans often exists as part of a mixed culture alongside other microbes and is influenced by their presence as well as the presence of QS molecules that they produce. In this study, a library of diploid homozygous transcriptional regulator knockout (TRKO) mutants were screened to identify strains capable of forming hyphae in the presence of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. We identified three strains that showed increased hyphae development compared to wild type C. albicans. The strains identified had deletions of the transcriptional regulating genes Orf19.3928, Orf19.2842 (GZF3), and Orf19.3865 (RFX1). These strains were tested for alterations of filamentation in liquid media, and biofilm formation. All three strains showed increased rates of biofilm formation compared to the wild type. Orf19.3928 showed altered response to farnesol, a marked in biofilm formation and no inhibition of filamentation when farnesol was present in liquid media. The GZF3 deletion strain showed enhanced filamentation with all three bacterial species while the RFX1 deletion strain showed increased filamentation only with E. coli and S. aureus. In spent media, GZF3 showed slight increases in filamentation in E. coli and S. aureus while RFX1 had moderate increases in filamentation in E. coli and S. aureus and slight increases with P. aeruginosa.

Objectives: The primary objective was to assess the impact of two denture fabrication techniques, conventional and CAD/CAM, on oral health-related quality of life (OHRQoL) and patient satisfaction in complete denture wearers. The secondary objective was to compare the level of microorganisms present on complete dentures from the two fabrication techniques. Methods: Twenty-eight completely edentulous subjects (16 men and 21 women, age range from 49 to 87 years old.), who had been edentulous for at least 6 months, were wearing ill-fitting complete dentures, or unsatisfied with their existing complete dentures were recruited. Subjects were randomized to conventional and computer-aided design/ computer-aided manufacturing (CAD/CAM) treatment groups. Subjects in both groups were given the OHIP-EDENT (Oral Health Impact Profile for Edentulous Patients) and patient satisfaction questionnaires to record the data at baseline and at 1 month post-delivery of the new prostheses. Plaque samples were collected from intaglio surfaces of maxillary complete dentures at 1 month post-delivery to culture for any colonization of bacteria and/or yeasts. Results: There was a significant reduction in OHIP-EDENT scores within both treatment groups at the 1 month follow-up (p < 0.05). There was also a significant reduction in almost all OHIP-EDENT domains scores at 1 month. Gender was significantly associated with OHIP-EDENT score at baseline (p = 0.0419) and at 1 month (p = 0.0152). Female subjects tend to have higher OHIP-EDENT scores than male subjects. There was no significant difference in patient satisfaction between treatment groups both at baseline and at the 1 month visit for almost all aspects of satisfaction (p> 0.05). Appearance of maxillary denture was the only significant difference in patient satisfaction across treatment groups (p = 0.0213). The comparisons of microbial counts showed no significant difference between treatment groups. Conclusions: There were no significant difference on oral health-related quality of life (OHRQoL) and patient satisfaction between two treatment groups at baseline and 1 month. There was no significant difference in microbial counts between two treatment groups.

Made available in DSpace on 2014-12-17T15:32:16Z (GMT). No. of bitstreams: 1 MarceloGV.pdf: 2007167 bytes, checksum: 5ee7e9c9bd56fd72fecb1874fb64a80e (MD5) Previous issue date: 2008-02-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed / A angiog?nese ? um mecanismo fundamental para o desenvolvimento tumoral, sendo utilizada para fins de diagn?stico diferencial e determina??o de progn?stico em v?rias neoplasias de cabe?a e pesco?o. Este trabalho se prop?s avaliar a atividade angiog?nica atrav?s da express?o imuno-histoqu?mica dos anticorpos anti-CD105 e anti-CD34 em 20 casos de hemangiomas e 20 casos de granulomas piog?nicos orais, al?m de averiguar a utilidade destes marcadores como um dos recursos de diagn?stico diferencial para estas duas les?es orais. Os resultados deste experimento demonstraram que n?o houve diferen?a estatisticamente significativa entre as m?dias de contagem microvascular (MVC) determinadas pelos os anticorpos anti-CD105 (p=0,803) e anti-CD34 (p=0,279). O n?mero m?dio dos vasos obtidos pela MVC nos esp?cimes de hemangiomas orais imunomarcados pelo anti-CD105 e anti-CD34 foram respectivamente 18,75 e 59,72, enquanto nos granulomas piog?nicos orais, o n?mero m?dio dos vasos obtidos pela MVC pelo anti-CD105 e anti-CD34 foram respectivamente 20,22 e 48,09. Foi verificado, tamb?m, que o CD34 foi mais efetivo na identifica??o de vasos sang??neos quando comparado com o CD105. Entretanto, faz-se necess?rio destacar, que o anticorpo anti-CD105 parece estar mais relacionado com a neoforma??o vascular. Em linhas gerais, este ensaio refor?a a participa??o dos fatores angiog?nicos na etiopatog?nese dos hemangiomas e granulomas piog?nicos orais, por?m os resultados mostraram que a quantifica??o da angiog?nese n?o pode ser utilizada como par?metro de diagn?stico diferencial entre as duas les?es analisadas

Made available in DSpace on 2014-12-17T15:32:17Z (GMT). No. of bitstreams: 1 GustavoPG.pdf: 468493 bytes, checksum: 5f74059b167ef7c7965d0eddca9dca0c (MD5) Previous issue date: 2006-05-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The aim of this study was to evaluate the clinical and pathological features of cases diagnosed as dentigerous cyst by the Department of Oral Pathology, School of Dentristy at the Federal University of Rio grande do Norte, attempting the possible correlation between histomorphological findings and epidemiological data contained at the files of the patients, in order to define a suggested variation of lesion named inflammatory dentigerous cyst. It was verified that dentigerous cyst are more frequently present in the earfy three decades of life, with the majority of cases occuring in the second decade (40,740/0 ), and also male (57,41%) and white patients (68,52%) were most affected. In relation to anatomic site, the dentigerous cyst was more prevalent at anterior maxila and posterior mandible, showing, usually, a slow growth pattem. The majority of lesions were asymptomatic and the radiographic observed was frequently na unilocular radiolucency. In regard to the histomorphological analysis, it was noticed that the lesions showed commonly a thin epithelium, with a capsule of fibrous connective tissue, richly vascularized and collagenized with an intense mononuclear inflammatory infiltrate. Finally, clinicopathological was performed and it was find out that cysts that showed a thick epithelium, with a high degree of vascularization and collagenization, intense inflammatory infiltrate in the cystic capsule, were located in the pre-molares region, in patients under 12 years old and the majority showing painfull sintomatology, properly, compatible with inflammatory dentigerous cyst. The findings of the present study indicate that, probably, there is a variant of the dentigerous cyst, and therefore, we suggest the denomination inflammatory follicular cyst for this entity / Este estudo teve como objetivo realizar uma analise clinicopatologica de casos diagnosticados como cisto dentigeno na Disciplina de Patologia Oral do Departamento de Odontologia da UFRN,enfatizando uma possivel correla??o entre os achados histomorfologicos e os dados epidemiologicos constantes nas fichas de solicita??o de exame histopatologico,no intuito de caracterizar uma possivel variante da les?o,denominada cisto dentigero de origem inflamatoria.Foi verificado que o cisto dentigero apresentou-se com maior frequencia nas tres primeiras decadas de vida,com maior numero de casos observados na segunda decada(40,74%);tendo sido o genero masculino o mais afetado,com 57,41% dos casos,e os pacientes leucodermas os mais acometidos com 68,52% da amostra total.A regiao anatomica mais atingida foi a anterior de maxila e a posterior de mandibula, sendo o padrao de crescimento lento o mais comumente observado.A maioia das lesoes apresentou-se assintomatica,e o aspecto radiografico frequentemente identificado foi o radiolucido inilocular.Quanto a analise histomorfologica,observou-se que as lesoes

Orientador: Edgard Graner / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-09T14:11:16Z (GMT). No. of bitstreams: 1 Agostini_Michelle_D.pdf: 6485719 bytes, checksum: f82ba343c6049746e2b63420116af03c (MD5) Previous issue date: 2007 / Resumo: O sistema ubiquitina-proteossomo degrada proteínas marcadas com etiquetas de Ub. A ubiquitinação é um processo reversível e moléculas de Ub podem ser desconjugadas pelas enzimas desubiquitinantes (DUBs), que evitam a degradação e aumentam a meia vida de seus substratos. A DUB USP2a foi identificada na próstata humana, é regulada por andrógenos e tem sua expressão aumentada em adenocarcinomas. USP2a protege a enzima ácido graxo sintase (FAS) da degradação, a qual é superexpressa em vários tipos de tumores, inclusive nos carcinomas espinocelulares (CECs) bucais. O objetivo deste trabalho foi estudar a expressão desta DUB e seu papel biológico em células derivadas de CECs bucais humanos. Foram detectados RNAs mensageiros para USP2a nas quatro linhagens celulares estudadas, principalmente nas linhagens SCC-4 e -15. Os níveis protéicos de USP2a foram semelhantes nas quatro linhagens, sendo ligeiramente maiores na SCC-9 e -25. Portanto, não foi encontrada uma correlação entre a quantidade de RNAs mensageiros e dos produtos protéicos de USP2a. Através de experimentos de imunofluorescência, demonstramos USP2a no citoplasma das células SCC-9, havendo uma concentração na região perinuclear em algumas células. A expressão forçada de USP2a nas células SCC- 9 não conferiu vantagem proliferativa, no entanto, a superexpressão de um duplomutante parece ter diminuído a proliferação. Ao contrário do que ocorre nas células LNCaP, a inibição da expressão de USP2a através de RNAi nas células SCC-9 causou discreta indução de apoptose. O tratamento das células SCC-9 com diferentes concentrações do fator de crescimento epidérmico (EGF) foi capaz de modular a expressão de USP2a, interferindo na quantidade de formas ubiquitinadas de FAS. Também foi investigada neste trabalho a possível interação entre USP2a e a proteína clatrina. De acordo com resultados prévios de experimentos realizados no laboratório do Dr. Massimo Loda, no Dana-Farber Cancer Institute, a cadeia pesada de clatrina é também substrato de USP2a. Clatrina é uma proteína que participa do processo de internalização e endocitose de proteínas localizadas na membrana plasmática. Demonstramos que USP2a e a cadeia pesada de clatrina estão co-localizadas no citoplasma de células AR-iPrEC e SCC-9 e que a produção de clatrina é regulada por andrógenos em células LNCaP. Houve uma maior produção de clatrina em células que superexpressam de forma estável USP2a. Um achado interessante foi que USP2a, além de presente no citoplasma, foi também encontrada na membrana plasmática de células LNCaP e o tratamento com EGF interferiu na localização sub-celular desta DUB, como ocorre com clatrina durante a endocitose. Estes resultados sugerem que USP2a participe do processo de endocitose mediada por clatrina / Abstract: The ubiquitin (Ub)-proteasome pathway controls cellular protein turnover by degrading targeted intracellular proteins tagged with poly-Ub chains. Ubiquitination is a reversible process and the deubiquitinating enzymes (DUBs) are proteases that specifically cleave off Ub from Ub-protein conjugates. They can act in a preproteasomal level removing the poly-Ub tag from specific substrates and preventing and modulating their degradation. The DUBs USP2a and USP2b were recently identified in the prostate of men and rats. USP2a is androgen-regulated, overexpressed in prostate cancer, and interacts with and stabilizes fatty acid synthase (FAS) and the protein murine double minute (Mdm2). FAS is overexpressed in several human malignancies, including oral squamous cell carcinoma, and is correlated with a poor prognosis for some tumors. Mdm2 is an Ub-protein ligase responsible for its own ubiquitination and ubiquitination of p53, that is degraded by the proteasome. When overexpressed in nontransformed cells USP2a exhibits oncogenic behavior both in vitro and in vivo and prevents apoptosis induced by chemotherapeutic agents. Considering that USP2a stabilizes FAS and Mdm2 and then protects tumoral cells from apoptosis, the purpose of the present study was to investigate the USP2a expression and its biological role in human oral squamous carcinoma cells. mRNAs for USP2a were detected in the four studied cell lines, mainly in SCC-4 and -15. The USP2a protein levels were similar in all cell lines, being slightly higher in SCC-9 and -25. By using immunofluorescence we showed that USP2a is located in the cytoplasm of SCC-9 cells and eventually concentrated around the nuclei. No significant differences were found in the proliferative rates of USP2a overexpressing SCC-9 cells, however, cells overexpressing mutant USP2a had lower proliferative potential. In contrast with LNCaP cells, USP2a silencing by siRNA slightly induced apoptosis. The treatment with different concentrations of EGF was able to modulate the USP2a expression in SCC-9 cells and change the amount of ubiquitinated forms of FAS. We also show in the present study experiments performed in the laboratory of Dr. Massimo Loda at the Dana-Farber Cancer Institute, in which the possible interaction between USP2a and clathrin was analyzed. Clathrin is involved in the internalization and endocytosis of proteins located in at the plasma membrane. Here we show that USP2a and clathrin heavy chain colocalize in the cytoplasm of AR-iPrEC and SCC-9 cells and that clathrin protein expression is regulated by androgens in LNCaP cells. We found higher amounts of clathrin in cells that stably express USP2a than in the controls. USP2a was found at the plasma membrane in LNCaP cells and after EGF stimulation a granular positivity for USP2a was observed in the cytoplasm. These results suggest that USP2a may have a role in the clathrin mediated endocytosis / Doutorado / Patologia

RESUMO Os índices de prevalência das anomalias dentárias, sua distribuição por sexo, idade, arcada e lado têm variado de um autor para outro, e também, de acordo com a população pesquisada. Esta pesquisa foi desenvolvida no município de Belém, onde foram avaliadas 500 radiografias panorâmicas, de crianças de ambos os sexos, com a finalidade de se identificar a ocorrência das seguintes anomalias : Anodontia, Taurodontia, Dentes não irrompidos, Microdontia, Macrodontia, Dentes supranumerários e Geminação. Foi objetivo desta pesquisa, a partir das radiografias analisadas, buscar a caracterização das crianças avaliadas, possibilitando o diagnóstico, o mais precoce possível, facilitando as soluções terapêuticas. A análise dos resultados aferidos permite inferir que a amostra pesquisada apresenta traços característicos. Foram analisadas 500 radiografias panorâmicas, de 240 crianças do sexo masculino e 260 crianças do sexo feminino, sendo encontrados 118 casos de anomalias, perfazendo um prevalência de 16%.De acordo com as anomalias pesquisadas encontrou - se as seguintes prevalências: Anodontia (5,4%), Taurodontia (1,0%), Dentes não irrompidos (4,2%), Microdontia (2,0%), Macrodontia (0,6%), Dentes supranumerários (2,4%) e Geminação (0,4%). / SUMMARY The rates of Dental prevalence of anomalies, its distribution per sex, age, arcade e side varies from author to author, and also according to the researched population. For this research was developed in the city of Belém where, 500 panoramic radiographies of children of both sexes were inspected in order to identify the happening of the following anomalies : Anodontia, Taurodontia, Unbroken out teeth, Microdontia, Macrodontia,Supernumerary teeth, Gemination. The purpose of this research, after the study of the radiographies, was to develop the haracterization of the appraised children in order to determine the therapeutic solutions.The analysis of the gauged results allows the conclusion that the researched sample presents characteristic features.There were found 118 cases of anomalies, completing a prevalence of 16%. According to the anomalies researched there were found the following prevalence rates : Anodontia ( 5,4% ), Taurodontia ( 1,0% ), Unbroken out teeth ( 4,2% ), Microdontia ( 2,0% ), Macrodontia ( 0,6% ) and Gemination ( 0,4% ).

Esta pesquisa aborda, a partir de uma perspectiva bioarqueológica comparativa, a problemática das mudanças nos padrões de subsistência associados à intensificação da agricultura e suas implicações no processo de complexificação social na costa dos Andes Centrais. Para tanto, se examinaram indicadores de patologia oral, estresse nutricional e isótopos estáveis, e outros dados paleodietéticos e arqueológicos de 09 populações pré-históricas da costa dos Andes Centrais datadas para o período Formativo (~3000-1 a.C.). Os resultados mostram que as dietas a predomínio de carboidratos são muito antigas na região, inclusive nos sítios litorâneos e que o processo de complexificação ocorreu em presença da agricultura como base econômica. As formações teocráticas do 3ro e 2do milênios a.C. floresceram baseadas na agricultura de tubérculos, leguminosas, árvores frutíferas e milho em menor quantidade (abaixo de 20%), apelando a técnicas agrícolas adaptadas às características de aridez dos vales da bacia do Pacífico. Uma drástica mudança na dieta costeira andina ocorreu entre 500-1 a.C., quando o milho passa ser o principal produto de subsistência ao nível regional em concomitância com o aparecimento de governos seculares. / From a comparative bioarchaeological perspective this research addresses the issue of changes in subsistence patterns associated with the intensification of agriculture on the coast of the Central Andes and their implications to the social complexity process. Markers of oral pathology and nutritional stress were examined, along with stable isotopes, and other paleodietetic and archaeological data of 09 prehistoric coastal populations dated to the Formative period (~3000-1 BC). The results show that the predominance of rich carbohydrate diets is very old in the region, also on shoreline settlements, and the process of complexity was based in agriculture as an economic basis. The theocratic societies of 3rd and 2nd millennium BC flourished based on agriculture of tubers, legumes, fruit trees and corn in smaller quantities (below 20%), using farming techniques highly adapted to the aridity of the Pacific basin valleys. A drastic change in the Andean coastal diet occurred between 500-1 BC, when the corn became the main regional staple concomitant to the appearance of secular governments

<p>A multitude of neurologic diseases are increasing in patients that both diminish quality and quantity of life. My dissertation research focused on unraveling the blood-brain barrier’s alterations (BBB), primarily in lung cancer brain metastases, the most common brain metastasis in patients. We optimized a reliable and reproducible mouse model for creating brain metastases using patient derived brain seeking cells of non-small lung cancer (NSCLC) using ultrasound-guided intracardiac injection. I then evaluated brain tissue with qualitative and quantitative immunofluorescence for individual components of the BBB. Using this experimental method, I was able to identify the specific shift of each BBB component over time in NSCLC brain metastases. I then used human brain metastases specimens to demonstrate the clinical relevance of my findings. These results show distinct alterations in the BBB, which have the potential for targeting therapeutic delivery to extend patient survival. I was also able to characterize a novel epithelial-mesenchymal (EMT) phenotype in vertebral metastases of NSCLC in our model, with features similar to those seen in human patients. Most recently, I analyzed patterns of paracellular permeability associated with each BBB component of NSCLC brain metastases which may provide direct passageways for therapeutic delivery. Altogether, this research offered foundational evidence for the future development of targeted novel therapeutics, including nanoparticles. Outside of the brain metastases field, we used an experimental framework to successfully characterize the BBB alterations in a traumatic brain injury model (bTBI). These findings provided the first description of this unique pathology and the framework for developing therapeutics in other neurologic diseases. Although my research work has focused on animal models of disease, future directions based on my research work include the developing a novel 3D BBB-on-chip device to enable high throughput novel therapeutic delivery through the BBB. Long-term, identifying targetable alterations in the restrictive BBB using <i>in vitro</i> and <i>in vivo</i> models provides a potential conduit for effective prevention and treatment of a myriad of neurologic diseases to prolong patient survival and quality of life.</p>