Magister Scientiae Dentium - MSc(Dent) / Ossifying fibroma (OF) is the most frequent of the three fibro-osseous lesions of the jaws. It occurs mostly in patients between the age of 20 and 40 years. Females are more commonly affected than males. Clinically, OF usually presents as a painless expansive intra-bony mass. Swelling and pain may be present in some cases while some lesions are discovered incidentally. Radiographically, OF is usually well-defined and unilocular or multilocular. Early lesions present as well-defined radiolucency that are small in size. Over time, the lesions tend to enlarge in size and become mixed radiolucent-radiopaque and finally become completely radiopaque. The aim of this study was to determine the clinical and radiological features of ossifying fibroma presenting at the Departments of Maxillo-Facial and Oral Surgery and Diagnostics and Radiology, University of the Western Cape Oral Health Centre as well as to assess its management and recurrence patterns. A retrospective case series analysis was performed of all histopathologically diagnosed ossifying fibroma cases available at the Departments of Maxillo-Facial and Oral Surgery and Diagnostics and Radiology at the Faculty of Dentistry, University of the Western Cape from 1976-2014. Patient's age, gender and ethnicity were recorded. The clinical presentation of the lesion as well as the history was analyzed. Radiographic features including density, size, shape, location, locularity and its effect on adjacent structures was noted. Management of each case and follow-up was also documented. A total 61 cases were included in the study. The majority of patients were females (63.9%) and below 40 years of age (73.9%). Few cases were symptomatic (29.5%) with an average period 22 months from first symptoms to presentation. The mandibular posterior region was most affected (55.5%) while larger lesions occurred more frequently in younger patients. Majority of lesions were radiopaque (49.2%) and had well-defined margins (93.6%). Most cases were managed by surgical curettage (68.2%). Following an average follow-up period of 20 months only one case recurred (recurrence rate =6.7%). In conclusion, the majority of the clinical and radiographic findings of ossifying fibroma were similar in South African patients as those of other populations. Differences include that the lesions in this population were more radio-opaque and larger in size than in the reported literature. Surgical curettage is an acceptable management protocol with low rate of recurrence.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Background: Carcinoembryonic antigen (CEA) in the pancreatic cystic fluid is the most important biomarker for differentiating mucinous from non-mucinous pancreatic cystic lesions (PCLs). However, recent studies have shown that glucose levels in pancreatic cystic fluid can discriminate mucinous from non-mucinous cysts. Aims: To perform a meta-analysis to determine the utility of intracystic fluid glucose of pancreatic mucinous cysts compared with intracystic CEA. Methods: We conducted a systematic review of the literature in the PubMed, OVID Medline, and Cochrane databases. This meta-analysis considers studies published up to October 2020. Results: Six studies comprising 506 patients were selected; 61.2% of the population was female. Of the 480 PCLs, 287 (59.7%) were mucinous. Pooled sensitivity and specificity of cystic fluid glucose levels for mucinous PCLs were 91% and 85%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 6.33 and 0.11, respectively. Pooled diagnostic odds ratio (DOR) was 60.94. The pooled area under the summary receiver operating characteristic (SROC) curve was 0.959. Pooled sensitivity and specificity of pancreatic cystic fluid CEA levels were 61% and 93%. The PLR and NLR were 8.51 and 0.40, respectively. Pooled DOR was 23.52, and the pooled area under the SROC curve was 0.861. Conclusion: Glucose has become a useful method and appears to be better than CEA for differentiating between mucinous PCLs and non-mucinous PCLs. We suggest that the analysis of glucose in PCLs be routinely performed for the differential diagnosis of these lesions. / Revisión por pares

Les maladies cardiovasculaires sont la première cause de mortalité dans le monde, et la maladie coronaire est responsable de la majorité de ces décès. L’infarctus du myocarde et l’AVC sont principalement causés par la rupture de plaques d’athérome vulnérables. Malgré les récentes avancées dans la prise en charge des patients, aucun outil non invasif n’est actuellement disponible en pratique clinique pour le diagnostic de ces lésions. Le laboratoire UMR_S1039 Radiopharmaceutiques Biocliniques a développé un agent d’imagerie innovant ciblant la molécule d’adhésion cellulaire VCAM-1, impliquée dans le processus inflammatoire qui caractérise les plaques vulnérables. 99mTc-cAbVCAM1-5 appartient à une nouvelle classe de radiotraceurs dérivés d’anticorps de camélidés possédant uniquement une chaine lourde dont le domaine variable est appelé nanobody. Les lésions athéromateuses aortiques ont été visualisées avec succès par imagerie non invasive (SPECT) chez un modèle de souris déficient pour le gène ApoE. L’objectif de ma thèse a été double : finaliser la caractérisation préclinique de cAbVCAM1-5 et transférer ce radiotraceur vers la clinique. Dans un premier temps, la sensibilité de 99mTc-cAbVCAM1-5 a été démontrée avec succès par l’utilisation de thérapies de référence (statine, ézétimibe). Ces résultats prometteurs nous ont permis d’évaluer le potentiel effet anti-athérogène de nouveaux agents thérapeutiques et d’initier le transfert en clinique de cet agent d’imagerie. cAbVCAM1-5 et l’intermédiaire de réaction utilisé pour son radiomarquage ont été produits selon les bonnes pratiques de fabrication (BPF). Ces deux produits ont été évalués et validés. De plus la méthode de radiomarquage a été optimisée dans la perspective de son transfert vers la clinique. L’étude de toxicité étendue à dose unique est en cours. A l’issue de cette thèse, le laboratoire INSERM U1039 dispose donc de tous les éléments nécessaires pour une demande d’autorisation de phase clinique I/IIa. / Cardiovascular diseases (CVD) are the leading causes of death worldwide, and Coronary Artery Disease (CAD) is responsible for the majority of CVD deaths. Myocardial infarction and stroke are mainly caused by the rupture of vulnerable atherosclerotic plaques. Despite recent advances in treatment and detection of CAD, no non-invasive tool is currently available for the diagnosis of vulnerable plaques. The laboratory UMR_S1039 Radiopharmaceutiques Biocliniques has recently developed a new radiotracer (99mTc-cAbVCAM1-5) targeted to the inflammatory marker Vascular Cell Adhesion Molecule 1 (VCAM-1) expressed in vulnerable plaques. 99mTc-cAbVCAM1-5 belongs to a new class of radiotracers derived from single domain antibodies (sdAb), or nanobodies, that are composed of the single variable domain of the heavy chain antibodies of camelidae. Aortic plaques have been successfully visualized noninvasively by SPECT in an Apolipoprotein E (ApoE) deficient mouse model of atherosclerosis. The objectives of my thesis were to complete the preclinical characterization of cAbVCAM1-5 and to transfer this innovative tool to the clinic. The sensitivity of 99mTc-cAbVCAM1-5 imaging has been successfully demonstrated using gold standard therapies (statin, ezetimibe). Those good results allowed us to employ this imaging agent for the evaluation of new therapeutics and to initiate the clinical translation of cAbVCAM1-5. The productions of cAbVCAM1-5 and of the tricarbonyl employed for its radiolabeling have been performed according to good manufacturing practices (GMP). Both products have been evaluated and validated. Furthermore, the radiolabeling method has been optimized to facilitate its clinical transfer. Single dose toxicity study is currently ongoing. At the end of this PhD fellowship, the U1039 Laboratory therefore possesses all required products and knowledge for the onset of a first in human clinical trial.

Acute myeloid leukemia(AML) is the most common acute leukemia among adults in the United states with approximately 19,940 people being diagnosed of this disease in 2020 and 11,180 deaths. It is a heterogenous group of malignancy characterized by clonal expansion of blast with myeloid lineage in the bone marrow, peripheral blood and/or other tissues. Our patient is a 79-year-old male who presented to the hospital with reports of sharp, throbbing low back pain for one month, moderately controlled with pain medications. He reported 5 lb. weight loss with decreased appetite over one month but denied other constitutional symptoms. MRI Lumbar spine revealed multiple foci of marrow signal abnormality compatible with extensive metastatic disease. CT chest, abdomen and pelvis did not show any lesions concerning for primary or metastatic malignancy. CBC revealed normal WBC count, platelet count and hemoglobin level (with macrocytosis, MCV 104.7). Initial work up including Vitamin B12 and folic acid level, TSH, SPEP/IFE, serum light chain ratio and quantitative immunoglobulins were within normal limits. Pathology from a CT guided bone biopsy of the L spine lesion was concerning for high grade myeloid neoplasm. Patient had a bone marrow biopsy done at another hospital which was read as most consistent with acute myeloid leukemia (AML) with monocytic differentiation, with findings of hypocellular marrow, extensive fibrosis with focal areas of large clusters of immature cells, positive for MPO, CD33, CD43 and CD 56, Ki-67 of 60-80%. Cytogenetics showed an abnormal male karyotype with trisomy 8. FISH was negative for other AML or MDS related abnormalities. Given the above findings of AML and advanced age, patient was started on treatment with hypomethylating agent Decitabine along with BCL-2 inhibitor, Venetoclax. A repeat bone marrow biopsy after two cycles of the above regimen revealed progressive disease with extensive fibrosis and 80-90% blast on a core biopsy sample. Due to poor response to above regimen, lack of effective treatment options in older patients with AML and declining functional status, decision was made to pursue best supportive care. AML usually presents with symptoms of fevers, fatigue, dyspnea or bleeding. Skeletal lesions are usually associated with a diagnosis of multiple myeloma, or other solid organ malignancies and rare in AML. Extra medullary involvement of AML is known to happen in 2.5%-9% of patients and is termed as Myeloid Sarcoma. Due to the low incidence, prospective study data is limited. This entity is treated similarly to AML, depending on risk stratification by cytogenetics, age and targetable mutations which also govern its prognosis. This case highlights the importance of increased awareness and high index of suspicion among medical providers regarding this atypical presentation of AML since if missed or misdiagnosed could delay treatment and lead to poor outcomes.

In this experiment, rats were administered nicotine (0.3 mg/kg) for 11 consecutive days before and after an electrolytic medial frontal cortex lesion. After drug administration ceased, rats were tested on two spatial memory tasks, the radial arm maze (RAM) and the Morris water task (MWT). Behavioral testing was arranged so that rats were tested on the RAM 1 day after drug administration followed by behavioral testing on the MWT 19 days after drug treatment, or tested on the MWT 1 day after drug administration followed by testing on the RAM 4 days after drug treatment. Results of MWT testing showed that regardless of the drug/behavioral testing interval, lesioned rats given nicotine demonstrated enhancement relative to saline-treated lesioned animals, but the effects were more robust 1 day after drug treatment had ceased. Nicotine-induced behavioral compensation after medial frontal cortex lesions appears to be time-dependent in animals behaviorally tested on the MWT. Results of RAM testing showed that there were no significant differences between lesioned groups at the 1-day drug/testing interval, although nicotine improved performance in non-lesioned rats compared to non-lesioned rats given saline. Four days after drug administration, nicotine improved performance in lesioned rats to the levels of non-lesioned rats given saline or nicotine. This result suggests that previous training on the MWT may have primed behavioral compensation produced by nicotine in medial frontal cortex lesioned rats behaviorally tested on the RAM.

No description available.

Rats were trained on a four-way shuttle box with a compound light-tone conditioned stimulus (CS) until they emitted 7 avoidance responses in 10 trials (7/10) prior to bilateral ablation of the visual cortex or sham surgery. On Day 5 after surgery, rats were cued with either the compound light-tone CS, the light or tone portion of the CS only, or had no exposure to the CS. On Day 10 after surgery, all animals were tested for avoidance retention under the same conditions as preoperative training. The findings indicate that following a lesion, cueing with the light-tone compound CS facilitates performance as does light alone. Cueing to the tone alone has no effect. In sham animals, only cueing with the light-tone CS was effective in enhancing avoidance retention. Results are interpreted as early and modality-specific sensory cueing may facilitate the recovery process.

Discrete electrolytic lesions were placed in the mesencephalic dorsal noradrenergic (DNE) bundle of 22 male Sprague-Dawley rats, and sham operations were performed on 14 control animals. Eight components of copulatory behavior were compared in 2 preoperative and 2 postoperative heterosexual mating tests. A significant postlesion decrease in the postejaculatory interval (PEI), number of intromissions, number of incomplete mounts and the ejaculation latency from the first intromission (ELI) occurred. Norepinephrine levels were significantly reduced in the hippocampus, amygdala and hypothalamus, but not in the preoptic area. The only statistically significant correlations between NE concentrations and behavior in the lesioned animals were negative (hippocampal NE with PEI and ELI). The results support the hypothesis that rostral midbrain lesions disinhibit some components of male rodent copulatory behavior, but suggest that a system or systems other than the DNE bundle may be responsible for this disinhibition.

Indiana University-Purdue University Indianapolis (IUPUI) / The “total-etch” or “etch-and-rinse” systems have been the gold standard of dental bonding for decades. However, these systems are very technique-sensitive and time-consuming compared to newer “self-etch” or “self-adhesive” systems and have been implicated in cases of postoperative sensitivity. The purpose of this study was to compare the effects of two surface treatment protocols (self-etch vs. selective-etch) on the clinical performance of a universal adhesive and resin composite in Class V non-carious cervical lesions (NCCLs). Thirty-three volunteer subjects (17 male; 16 female; age range = 20 to 75 years) having at least two NCCLs were selected from patients of record at Indiana University School of Dentistry. Each subject received one resin composite restoration (Tetric EvoCeram, Ivoclar Vivadent) utilizing a self-etch (SfE) universal adhesive (Adhese Universal, Ivoclar Vivadent) with no separate enamel etching and another restoration utilizing adhesive and selective enamel etching (SelE) with 37% phosphoric acid (H3PO4). Both the adhesive and composite were placed following the manufacturer’s instructions. The two techniques were compared for differences in sensitivity, retention, marginal discoloration, marginal adaptation, and clinical acceptability at baseline and 6 months using the Cochran-Mantel-Haenszel tests for stratified, ordered categorical outcomes. Seventy-four restorations (37 SfE, 37 SelE) in 30 volunteers were evaluated at 12 months. No significant differences were found between the SfE and SelE groups for any variable at the 12-month recall (p>0.21). Retention was 100% at 12 months for both groups. Marginal adaptation was significantly worse at 12 months than at baseline for SelE (p=0.0163), but there was no difference for SfE (p=0.08). Sensitivity improved significantly from baseline to 12 months for both SelE (p=0.0113) and SfE (p=0.0128). The results obtained from this study are comparable to results observed in similar studies. Like similar studies involving self-etch adhesives in non-carious cervical lesions, our study showed no restorations lost to caries and excellent retention. The deterioration of selective-etch dentin margins was a result that differed from similar studies. A likely explanation for this finding would be the difficulty of controlling precise placement of phosphoric acid gel, causing undesired etching of dentin; this could result in suboptimal bonding to dentin. This report on 12-month data for a two-year study indicates significantly reduced sensitivity for both the SelE and SfE groups, and deterioration of SelE marginal adaptation. No decreases in retention, marginal discoloration, or clinical acceptability were observed in either group.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: Non-carious cervical lesions (NCCLs) can be defined as the loss of dental hard tissue near the cemento-enamel junction without bacterial involvement. Abrasion, erosion and abfraction have been mentioned as common etiological factors of NCCLs. Abrasion is the loss of tooth structure due to friction by materials such as toothbrushes or abrasives in toothpaste. In contrast, dental erosion is the loss of tooth structure driven by acids. Abfraction, on the other hand, starts due to the weakening of the tooth structure in areas of concentrated stress as a result of cuspal flexure from heavy and repeated occlusal loading, which progresses to dental hard-tissue loss. Purpose: The present study focused on the abrasion aspect of NCCLs. Specifically, it aimed to investigate the influence of dentifrice abrasivity and toothbrush stiffness on the development of NCCLs in vitro Hypothesis: NCCL development is affected by both the abrasive level of the dentifrice and the stiffness of the toothbrush, as well as their interaction. Materials and Methods: A total of 288 extracted human upper first premolars, free of any dental caries and root defects, were selected. The teeth were be cleaned with a hand periodontal scaler and randomly assigned into twelve groups (total of 24 teeth/group). Specimens were brushed in an automated toothbrushing machine, using simulated toothpaste slurries of varying abrasivity and toothbrushes of varying stiffness. This study examined three experimental factors: 1. Toothpaste abrasivity, at four levels: high, medium, low, and non-abrasive slurry (as negative control); 2. Toothbrush stiffness, at three levels: soft, medium, and hard; 3. Toothbrushing cycles at three levels: baseline, 35k, and 65k strokes. Specimens were analyzed by optical profilometry at baseline and after each brushing level. The response variable was the dentin volumetric loss, in mm3. All toothbrushes caused significantly higher tooth wear when associated to the high abrasive slurry, compared to medium- and low-abrasive slurries. Medium- caused more tooth wear than low-abrasive slurry, which in turn led to more tooth wear than the control. Hard and medium toothbrushes were not significantly different, but both caused significantly higher volumetric loss than Soft toothbrushes. There were no differences among toothbrushes, when used with the non-abrasive (control) and low- abrasive slurries. Overall, 35k strokes resulted in significantly less tooth volumetric loss than 65k.