Neurological disorders present a significant challenge in global health. With the increasing availability of imaging datasets and the development of precise machine learning models, early and accurate diagnosis of neurological conditions is a promising and active area of research. However, several characteristic factors in neurology domains, such as heterogeneous imaging, inaccurate labels, or limited data, act as bottlenecks in using deep learning on clinical neuroimaging. Given these circumstances, this dissertation attempts to provide a guideline, proposing several methods and showcasing successful implementations in broad neurological conditions, including epilepsy and neurodegeneration. Methodologically, a particular focus is on comparing a two-dimensional approach as opposed to three-dimensional neural networks. In most clinical domains of neurological disorders, data are scarce and signals are weak, discouraging the use of 3D representation of raw scan data. This dissertation first demonstrates competitive performances with 2D models in tuber segmentation and AD comorbidity detection. Second, the potentials of ensemble learning are explored, further justifying the use of 2D models in the identification of neurodegeneration. Lastly, CleanNeuro is introduced in the context of 2D classification, a novel algorithm for denoising the datasets prior to training. CleanNeuro, on top of 2D classification and ensemble learning, demonstrates the feasibility of accurately classifying patients with comorbid AD and cerebral amyloid angiopathy from AD controls. Methods presented in this dissertation may serve as exemplars in the study of neurological disorders using deep learning and clinical neuroimaging. Clinically, this dissertation contributes to improving automated diagnosis and identification of regional vulnerabilities of several neurological disorders on clinical neuroimaging using deep learning. First, the classification of patients with Alzheimer’s disease from cognitively normal group demonstrates the potentials of using positron emission tomography with tau tracers as a competitive biomarker for precision medicine. Second, the segmentation of tubers in patients with tuberous sclerosis complex proves a successful 2D modeling approach in quantifying neurological burden of a rare yet deadly disease. Third, the detection of comorbid pathologies from patients with Alzheimer’s disease is analyzed and discussed in depth. Based on prior findings that comorbidities of Alzheimer’s disease affect the brain structure in a distinctive pattern, this dissertation proves for the first time the effectiveness of using deep learning on the accurate identification of comorbid pathology in vivo. Leveraging postmortem neuropathology as ground truth labels on top of the proposed methods records competitive performances in comorbidity prediction. Notably, this dissertation discovers that structural magnetic resonance imaging is a reliable biomarker in differentiating the comorbid cereberal amyloid angiopathy from Alzheimer’s disease patients. The dissertation discusses experimental findings on a wide range of neurological disorders, including tuberous sclerosis complex, dementia, and epilepsy. These results contribute to better decision-making on building neural network models for understanding and managing neurological diseases. With the thorough exploration, the dissertation may provide valuable insights that can push forward research in clinical neurology.

A chronic hyperglycemic state often results in neuropathological complications such as peripheral diabetic neuropathy (PDN). PDN is a debilitating medical condition that impacts over half of the US population with diabetes. In this study, we used the model organism Caenorhabditis elegans to determine that glucose-supplemented diet leads to an increased rate of intrauterine egg hatching (IUEH) and the reduction of dopamine and serotonin is sufficient to suppress the glucose-induced IUEH. Moreover, in this research demonstrates that a glucose-supplemented diet impacts serotonin and dopamine-associated behaviors. Additionally, we demonstrate that a diet rich in glucose impacts the structure of the serotonergic neurons HSN and NSM. These findings highlight the utility of the model organism C. elegans in elucidating the impact of a glucose-supplemented diet on the nervous system. Finally, these studies show that a glucose-supplemented diet impacts transgenerational and intergenerational phenotypes as well as changes in the transcriptional profile of subsequent generations.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-β peptide (Aβ) as neuritic plaques in the brain. The short Aβ peptide is derived from a large transmembrane precursor protein, APP. Two different proteolytic enzymes, BACE1 and the gamma-secretase complex, are responsible for cleaving Aβ peptide from APP through an intricate processing pathway. Dysregulation of APP and BACE1 levels leading to excess Aβ deposition has been implicated in various forms of AD. Thus, a major goal in this dissertation was to discover novel regulatory pathways that control APP and BACE1 expression as a means to identify novel drug targets central to the Aβ-generating process. MicroRNAs (miRNA) are short, non-coding RNAs that act as post-transcriptional regulators of gene expression through specific interactions with target mRNAs. Global analyses predict that over sixty percent of human transcripts contain evolutionarily conserved miRNA target sites. Therefore, the specific hypothesis tested was that miRNA are relevant regulators of APP and BACE1 expression. In this work, several specific miRNA were identified that regulate APP protein expression (miR-101, miR-153 and miR-346) or BACE1 expression (miR-339-5p). These miRNAs mediated their post-transcriptional effects via interactions with specific target sites in the APP and BACE1 transcripts. Importantly, these miRNA also altered secretion of Aβ peptides in primary human fetal brain cultures. Surprisingly, miR-346 stimulated APP expression via target sites in the APP 5’-UTR. The mechanism of this effect appears to involve other RNA-binding proteins that bind to the APP 5’-UTR. Expression analyses demonstrated that these miRNAs are expressed to varying degrees in the human brain. Notably, miR-101, miR-153 and miR-339-5p are dysregulated in the AD brain at various stages of the disease. The work in this dissertation supports the hypothesis that miRNAs are important regulators of APP and BACE1 expression and are capable of altering Aβ homeostasis. Therefore, these miRNA may possibly serve as novel therapeutic targets for AD.

Today, unlike yesterday we talk about Moral Regeneration amongst the Vhavenḓa youth of today and throughout the whole world. Strategies of combating this monster that is snatching our youth are recommended in this study. The problem dealt with in this study is the issue of Moral degeneration amongst the youth which needs to be regenerated. There are many causes of moral degeneration amongst the youth discussed in this study which are accompanied by the remedial strategies. As a way forward in this study, observations of researchers and scholars on how to find the solution about moral degeneration that has impacted on the lives of Vhavenḓa youth and other youth of today around the globe were focused on. The literature review in this study was based more on issues that are linked to Indigenous Knowledge Systems as discussed by various scholars. This study used the qualitative research methodology though quantitative minimally. The sampling of data was more purposive though there were cases of convenience and snowballing so as to get more data. Data for this research study was collected through questionnaires and interviews from a host of interviewees. This data was analysed using open and axial coding. The findings were grouped or categorised into major themes in terms of selective coding. Reasons behind the findings were explained too. Finally, consequences, implications for further study and also recommendations were indicated. / African Languages / D. Litt. et Phil. (African languages)

<p>Cilj ovog istraživanja je bio da se utvrdi da li postoji razlika u debljini makule kod pacijenata sa glaukomom otvorenog ugla (POAG) u odnosu na zdravu populaciju i u zavisnosti od stepena progresije bolesti, kao i da se utvrdi da li postoji povezanost između promene debljine makule i stepena o&scaron;tećenja vidnog polja i debljine peripapilarnog sloja nervnih vlakana u zavisnosti od stepena progresije bolesti. Materijal i metode: U ovu kliničku prospektivnu studiju je uključeno 186 pacijenata. Na osnovu kliničkog nalaza formirane su tri grupe. Prva grupa (kontrolna &ndash; grupa zdravih): 68 pacijenata bez očnih oboljenja, sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.9, intraokularnim pritiskom (IOP) &le; 21 mmHg, normalnim odnosom ekskavacije i povr&scaron;ine glave vidnog živca i normalnim nalazom vidnog polja. Druga grupa (rani glaukom): 78 pacijenata sa klinički dijagnostikovanim primarnim glaukomom otvorenog ugla (sa karakterističnim o&scaron;tećenjem glave vidnog živca i sloja nervnih vlakana retine i kod kojih je srednja vrednost devijacije standardne automatske perimetrije MD &gt; -6 dB, prema Hodap klasifikaciji), bez drugih očnih ili sistemskih oboljenja, koja bi imala uticaj na nastanak glaukoma i sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.5. Treća grupa (glaukom srednjeg stepena): 40 pacijenata sa klinički dijagnostikovanim primarnim glaukomom otvorenog ugla (sa karakterističnim o&scaron;tećenjem glave vidnog živca i sloja nervnih vlakana retine i kod kojih je srednja vrednost devijacije standardne automatske perimetrije -6 dB &gt; MD &gt; -12 dB, prema Hodap klasifikaciji), bez drugih očnih ili sistemskih oboljenja, koja bi imala uticaj na nastanak glaukoma i sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.5. Svim pacijentima je bio urađen kompletan oftalmolo&scaron;ki pregled, kompjuterizovano vidno polje (Humphrey Field Analyzer, Carl Zeiss Meditec, Jena, Germany, SITA Standard, test C 24-2) i optička koherentna tomografija sloja nervnih vlakana peripapilarno i u predelu makule (SOCT Copernicus HR, Optopol Tech. SA, Zawiercie, Poland). Rezultati: Perifovea i parafovea, pokazuju statistički značajno smanjenje debljine i zapremine sloja nervnih vlakana u odnosu na stepen progresije glaukoma otvorenog ugla, pri čemu je ono nagla&scaron;enije u perifovei (p&lt;0,05). U svim segmentima makule (TPeriF, IPeriF, SPeriF, NPeriF, TParaF, SParaF, IParaF i NParaF) dolazi do smanjenja debljine i zapremine sloja nervnih vlakana sa progresijom bolesti (p&lt;0,05). Segmenti makule TPeriF, IPeriF, a potom i SPeriF, prema navedenom redosledu, predstavljaju segmente sa najvećim potencijalom za predikciju ranih glaukomskih o&scaron;tećenja s obzirom na uočeno najveće smanjenje debljine i zapremine nervnih vlakana (p&lt;0,05). Segmenti makule SParaF i NParaF predstavljaju segmente sa najvećim potencijalom za predikciju napredovanja glaukomskih o&scaron;tećenja srednjeg stepena s obzirom na uočeno najveće smanjenje debljine i zapremine nervnih vlakana (p&lt;0,05). Debljina RNFL glave vidnog živca se statistički značajno smanjuje sa progresijom bolesti u svim posmatranim segmentima (p&lt;0,05). Međusobni odnos između grupe zdravih i grupe pacijenata sa ranim glaukomom ukazuje da je statistički značajno smanjenje debljine RNFL prisutno u svim segmentima osim u segmentima P3 i P4 (p&gt;0,05). Merenja debljine RNFL u segmentu P6 imaju najbolji potencijal za predikciju ranog glaukoma s obzirom na najizraženije smanjenje debljine nervnih vlakana upravo u ovom segmentu (p&lt;0,05). Merenja debljine RNFL u segmentu P1 ima najbolji potencijal za predikciju dalje progresije bolesti. Debljina sloja nervnih vlakana makule srazmerna je smanjenju debljine RNFL na glavi vidnog živca, pri čemu je ona uočljivija na nivou segmenata koji su okarakterisani kao dobri prediktori za nastanak, odnosno progresiju bolesti (P6 sa IPeriF i TPeriF, odnosno P1 sa SPeriF), &scaron;to dodatno nagla&scaron;ava njihovu važnost u dijagnostici glaukoma otvorenog ugla. Debljina makule kod pacijenata sa glaukomom otvorenog ugla je opisana umerenom do dobrom povezano&scaron;ću sa stepenom o&scaron;tećenja vidnog polja, pri čemu je ona najjača kod TPeriF, IPeriF i SPeriF segmenata i srazmerna je stepenu o&scaron;tećenja vidnog polja. Koeficijenti korelacije između vrednosti srednje devijacije vidnog polja i debljine RNFL, odnosno&nbsp; sloja nervnih vlakana makule, pokazuju snažniju povezanost u odnosu na parametre dobijenog smanjenja debljine nervnih vlakana u makuli, &scaron;to otvara mogućnost za dalja istraživanja. Segmenti glave vidnog živca i makule, koji su pokazali najbolju diskriminaciju u smislu predikcije nastanka POAGa, kao i oni koji sugeri&scaron;u na njegovu progresiju, sme&scaron;teni su na lokacijama koje su međusobno povezane opisanim prirodnim tokom nervnih vlakana.&nbsp; Zaključak: Optička koherentna tomografija makule je važna pomoćna metoda u dijagnostici glaukoma kojom je moguće izdvojiti pacijente sa ranim glaukomom u odnosu na zdravu populaciju, odnosno utvrditi progresiju glaukoma otvorenog ugla.</p> / <p>All patients underwent complete ophthalmologic examination, SAP (Humphrey Field Analyzer, Carl Zeiss Meditec, Jena, Germany, SITA Standard, test C 24-2) and optical coherent tomography scans of RNFL and macula (SOCT Copernicus HR, Optopol Tech. SA, Zawiercie, Poland). Results: Perifoveal and parafoveal nerve fiber layer have shown significant reduction of thickness and volume compared to stage of POAG progression, where perifovea showed higher significance (p&lt;0,05). All macular segments (TPeriF, IPeriF, SPeriF, NPeriF, TParaF, SParaF, IParaF i NParaF) showed reduction in thickness and volume compared to disease progression (p&lt;0,05). Macular segments TPeriF, IPeriF, as well as SPeriF, represent segments with highest potential to predict early glaucomatous damage according to the most significant reduction of nerve fiber layer thickness and volume (p&lt;0,05). Macular segments SParaF and NParaF represent segments with highest potential to predict progression of POAG according to the most significant reduction of nerve fiber layer thickness and volume (p&lt;0,05). Optic nerve head (ONH) RNFL thickness showed reduction compared to POAG progression in all segments (p&lt;0,05). All ONH segments except P3 and P4 showed significant reduction of RNFL comparing control group to early glaucoma group patients (p&gt;0,05). ONH segment P6 was found to be the highly specific for early glaucoma prediction according to the most significant reduction of RNFL thickness (p&lt;0,05), while segment P1 was found to have highest potential for POAG progression. Macular nerve fiber layer thickness reduction follows ONH RNFL thickness reduction and there is mutual relation between both macular and ONH segments (P6 to IPeriF and TPeriF, P1 to SPeriF) with highest specificity for early defects and POAG progression. It was shown that macular thickness changes have moderate to good correlation with visual filed changes and it was highest in TPeriF, IPeriF and SPeriF segments. This correlation was found to be higher in macula then in ONH RNFL thickness changes, compared to visual field changes. Both macular and ONH RNFL segments, which were found to have highest specificity to POAG prediction and progression, are located in areas which mutually connect following natural course of nerve fiber layer between them. Conclusion: Optical coherence tomography of macula represents important ancillary method in POAG diagnosis and follow up, allowing to differentiate between early glaucoma patients and healthy individuals, as well as to determine progression of glaucomatous disease.</p>

<p>Akrilamid je toksična hemijska supstanca koja ima vrlo &scaron;iroku primenu u hemijskoj industriji, a 2002. godine otkriveno je njegovo prisustvo u namirnicima bogatim skrobom koje se pripremaju na visokim temperaturama. U poslednjh desetak godina primećen je veliki porast gastrointestinalnih tegoba u ljudskoj populaciji. Cilj istraživanja bio je ispitati patohistolo&scaron;ke promene u tkivu želuca pacova soja Wistar izazvanih peroralnim aplikovanjem akrilamida i na taj način povući paralelu sa mogućim gastrointestinalnim tegobama nastalim kao posledica konzumiranja hrane bogate akrilamidom. U istraživanju je ispitivano 6 grupa od po 5 eksperimentalnih životinja (pacovi soja Wistar). Dve kontrolne grupe kojima je peroralno aplikovana destilovana voda i koje su žrtvovane posle 24h i 72h; dve eksperimentalne kojima je peroralno aplikovan akrilamid u dnevnoj dozi od 25 mg/kg i koje su žrtvovane posle 24h i 72h; dve eksperimentalne grupe kojima je peroralno aplikovan akrilamid u dnevnoj dozi od 50 mg/kg i koje su žrtvovane posle 24h i 72h. Na histolo&scaron;kom materijalu tkiva želuca primenjena je kvalitativna histolo&scaron;ka analiza pod svetlosnim mikroskopom, semikvantitativna procena tipa mucina u epitelnim ćelijama sluznice želuca, prisustvo limfocita i granulocita u sluznici želuca, stereolo&scaron;ka merenja pojedinih kompartmana zida želuca, linearna merenja broja i veličine ganglijskih ćelija u Maissner-ovom i Auerbach-ovom nervnom pleksusu, kao i broj mastocita u lamini propriji sluznice i podsluznici želuca. Dobijene vrednosti merenih parametara su potom statistički obrađene. Nastale promene na tkivu želuca pacova soja Wistar se ogledaju u vidu blagog direktnog o&scaron;tećenja povr&scaron;nog epitela sa propratnom blagom inflamatornom reakcijom i blagom degranulacijom mastocita. U Maissner-ovom i Auerbach-ovom nervnom pleksusu su smanjene volumenske gustine nervnih vlakana i ganglijskih ćelija, kao i broj i veličina ganglijskih ćelija. Direktno toksično delovanje na epitel dovodi do posledične obnove epitela, te je potvrđeno prisustvo nezrelijih oblika mukoproduktivnih ćelija koje sadrže kisele, AB pozitivne mucine. Ispitani inflamatorni i degenerativni parametri pokazuju pozitivnu korelaciju u odnosu na dozu i/ili dužinu ekspozicije akrilamidu. Primena akrilamida peroralno pokazala je da postoje patohistolo&scaron;ke promene na tkivu želuca u vidu direktnog toksičnog o&scaron;tećenja epitela, inflamatorne reakcije i o&scaron;tećenja nervnih pleksusa. Poznavanjem mehanizma delovanja ove toksične materije moguće je primeniti adekvatnu prevenciju u ishrani i izvr&scaron;iti odgovarajući izbor terapijskih metoda.</p> / <p>Acrylamide is a toxic chemical substance with wide implementation in chemical industry. In 2002 it was discovered the presence of acrylamide in foods rich in starch which are prepared at high temperatures. In the last ten years there is a large increase in gastrointestinal illnesses in human population. The aim of this study was to investigate the histopathological changes in the gastric tissue in Wistar rats induced with injection of oral acrylamide and thus draw a parallel with possible gastrointestinal problems arising as a result of the consumption of foods rich in acrylamide. The research was carried out 6 groups of 5 experimental animals (Wistar rats). Two control groups that are orally concomitant application of distilled water and which were sacrificed after 24h and 72h; two experimental groups which are orally administrated acrylamide in a daily dose of 25 mg / kg and that were sacrificed after 24h and 72h; two experimental groups which were orally administrated acrylamide in a daily dose of 50 mg / kg and that were sacrificed after 24h and 72h. On histological gastric tissue material is applied qualitative histological analysis by light microscopy, semi-quantitative assessment of the type of mucin in epithelial cells of the stomach lining, the presence of lymphocytes and granulocytes in gastric mucosa, stereological measurements of individual compartments of the stomach wall, linear measuring the number and size of ganglion cells in the Maissner and Auerbach&#39;s nerve plexus, and the number of mast cells in the lamina propria of the mucosa and in the submucosis of the stomach. Obtained values of measured parameters were statistically processed. Histological changes in the stomach tissue of Wistar rats are seen as a direct slight damage of the surface epithelium, with accompanynig mild inflammatory reaction and the degranulation of mast cells. The Meissner&#39;s and Auerbach&#39;s nerve plexus decreased volume density of nerve fibers and ganglion cells, as well as the number and size of the ganglion cells. Directly toxic effect on epithelium leads to the result of the reconstruction of the epithelium, which is confirmed by the presence of immature form of mucoproductive cells which contain acid, AB positive mucins. Examined inflammatory and degenerative parameters show a positive correlation with respect to dose and / or a time of exposition to acrylamide. Acrylamide oral application revealed that there are histologic changes in the stomach tissue in the form of a direct toxic damage to the epithelium, inflammatory reaction and damage to the nerve plexus. Knowing the mechanism of action of these toxic substances allows to apply adequate prevention in nutrition and make an appropriate choice of therapeutic methods.</p>

La paralysie cérébrale (PC) regroupe un ensemble varié de troubles moteurs, sensoriels et cognitifs, liés à des lésions de la substance blanche (i.e. leucomalacie périventriculaire, PVL) survenant, le plus souvent, après un épisode hypoxo-ischémique autour de la naissance. Afin de reproduire la PVL chez l'animal, nous utilisons une ischémie prénatale (PI) qui induit des lésions des substances blanche et grise. Les rats ischémiés développent des déficits cognitifs visuo-spatiaux et une hyperactivité, également observés chez les patients atteints de PC, liés à des lésions du cortex entorhinal, préfrontal et cingulaire. La PI n'induit que des troubles locomoteurs modérés associés à des signes de spasticité, et une atteinte anatomique et fonctionnelle du cortex somesthésique primaire (S1), tandis que le cortex moteur (M1) reste intact. Ainsi, la PI reproduit les symptômes observés chez les enfants et adultes nés prématurément. La présence de mouvements spontanés anormaux au cours de la 1ère année conduisant à la PC suggère une implication de l'expérience sensorimotrice anormale dans le développement de cette pathologie. La combinaison d'une restriction sensorimotrice (SMR) durant le développement et de la PI induit des troubles cognitifs atténués mais une hyperactivité importante. Les rats combinant PI et SMR présentent des déficits posturo-moteurs drastiques et une spasticité, associés à une dégradation des tissus musculo-squelettiques, comparables à ceux observés chez les patients. Ces troubles moteurs, associés à une désorganisation importante des cartes corticales dans S1 et M1, suggèrent un dysfonctionnement important des boucles d'intégration sensorimotrice. / Cerebral palsy (CP) corresponds to various motor, sensory and cognitive disorders related to white matter damage (i.e. periventricular leucomalacia, PVL) often occurring after perinatal hypoxic-ischemic events. To reproduce PVL in rodents, we used a prenatal ischemia (PI) that induces white and gray matter damage. The ischemic rats exhibit visual-spatial cognitive deficits and hyperactivity, as observed in patients with CP, related to lesions of entorhinal, prefrontal and cingular cortices. Only mild locomotor disorders are induced by PI, associated to signs of spasticity, along with anatomical and functional degradation in the primary somatosensory cortex (S1), while the primary motor cortex (M1) remains unchanged. Thus, PI recapitulates the main symptoms found in children born preterm. Abnormal spontaneous movements (i.e. general movements) observed in infants who develop CP later on suggest that abnormal sensorimotor experience during maturation is key in the development of this catastrophic disease. The combination of a sensorimotor restriction (SMR) and PI in animal induces fewer cognitive deficits but still hyperactivity. Such a combination leads to severe postural and motor disorders, and spasticity, associated with musculoskeletal pathologies, as observed in patients with CP. In addition to motor disorders, drastic topographical disorganization of cortical maps in S1 and M1 suggest a major dysfunction of sensorimotor loops.

Hyperfosforylering av biomarkörproteinet Tau förekommer i flera neurodegenerativa sjukdomar som kallas Taupathies. Proteinets huvudfunktion i människokroppen är att modulera flexibilitet och stabilitet för axonal-mikrotubulin. I Taupathies utlöser hyperfosforyleringen av Tau instabilitet och neurodegenerationen. I dagens läge kan hyperfosforylering av treonin 217 (P217) endast mätas i hjärnan. I den här studien undersöks hyperfosforyleringen av treonin 217 (P217). I syfte att se om nivåerna av P217 är mätbara i cerebrospinalvätska (CSV) och i blodet. Samt för att evaluera hur nivåer av P217 förändras i olika Taupathies, genom att testa hjärnprover från friska kontroller och olika Taupathies. Studien görs för att öka kunskapen om effekten av hyperfosforylering av treonin 217 i Taupathies och för att bidra med en ny provtagningsmetod för P217. Simoa HD-1 Analyzer var instrumentet som användes för analyserna av P217. Det är ett instrument som kan upptäcka onormala nivåer av biomarkörer genom kvantifiering, med hjälp av antikroppar och ett enzym. Enzymet kallas Streptavidin β-galaktosidas och omvandlar en befintlig P217-molekyl i proven till en fluorescerande produkt. Genom Simoa HD-1 Analyzer utvecklades en ultrasensitiv analys med antikropparna P217 och Tau 12, som kunde upptäcka mycket låga nivåer av P217 i hjärnan, CSF och i blod. Förändring av P217-nivåer hittades även i olika Taupathies. De Taupathies med de högsta nivåerna av P217 var Progressiv supranukleär pares, Corticobasal degeneration och Globular glial Taupathies. / Hyperphosphorylation of the biomarker protein Tau occurs in many neurodegenerative diseases called Taupathies. The proteins main function in the human body is to modulate flexibility and stability for axonal microtubules. In Taupathies the hyperphosphorylation of the Tau triggers instability and neurodegeneration. Nowdays hyperphoshorylation on threonine 217 (P217) can only be measured in the brain. In this study the hyperphoshorylation on the phosphorylation site of threonine 217 (P217) is examined. In aim to see if levels of P217 is measurable in cerebrospinal fluid (CSF) and in blood. As well to evaluate how P217 variate in different Taupathies, through the use of brain samples from healthy controls and different Taupathies. The study is made for the purpose of enhancing the pure knowledge about the effect of hyperphosphorylation on threonine 217 in Taupathies and to contribute with a new sampling method for P217. Simoa HD-1 Analyzer was the key instrument of the analyses of P217. It’s an instrument which can detect abnormal levels of biomarkers through quantification, with help of antibodies and an enzyme. The enzyme is called Streptavidin β-galactosidase and converts an existing P217 molecule in the samples to a fluoresce product. Through the use of Simoa HD-1 Analyzer an ultrasensitive assay with antibodies P217 and Tau 12 was developed which could detect very low levels of P217 in brain, CSF and in blood. Variation of P217 levels was also found in different Taupathies. The Taupathies with the highest levels of P217 was Progressive supranuclear palsy, Corticobasal Degeneration and Globular glial Taupathies.

Para avaliar a eficácia do método de pré-degeneração em nervos ciáticos de ratos durante diferentes intervalos de tempo, foram realizados estudos histomorfométricos de cortes laminares obtidos ao nível do enxerto e no segmento distal do nervo receptor. Os resultados foram comparados com a técnica convencional de enxertia nervosa. Verificou-se que o tempo de pré-degeneração interfere na regeneração de novos axônios e que o período mais adequado para sua utilização situou-se ao redor de 2 semanas no modelo experimental adotado / In order to evaluate the efficacy of a predegeneration method in rat sciatic nerves during different periods of time, histomorphometric studies were performed at the graft and distal segment sites of the recipient nerves. The results were compared with the conventional nerve grafting technique. It was shown that the period of predegeneration interfered in the regeneration of new axons and the most favorable time for its use is around 2 weeks, in this experimental model