University of Lisbon

About: University of Lisbon is a education organization based out in Lisbon, Lisboa, Portugal. It is known for research contribution in the topics: Population & European union. The organization has 19122 authors who have published 48503 publications receiving 1102623 citations. The organization is also known as: Universidade de Lisboa & Lisbon University.

Survival and reasons for failure of amalgam versus composite posterior restorations placed in a randomized clinical trial

Abstract: Background Failure of dental restorations is a major concern in dental practice. Replacement of failed restorations constitutes the majority of operative work. Clinicians should be aware of the longevity of, and likely reasons for the failure of, direct posterior restorations. In a long-term, randomized clinical trial, the authors compared the longevity of amalgam and composite. Subjects, Methods and Materials The authors randomly assigned one-half of the 472 subjects, whose age ranged from 8 through 12 years, to receive amalgam restorations in posterior teeth and the other one-half to receive resin-based composite restorations. Study dentists saw subjects annually to conduct follow-up oral examinations and take bitewing radiographs. Restorations needing replacement were failures. The dentists recorded differential reasons for restoration failure. Results Subjects received a total of 1,748 restorations at baseline, which the authors followed for up to seven years. Overall, 10.1 percent of the baseline restorations failed. The survival rate of the amalgam restorations was 94.4 percent; that of composite restorations was 85.5 percent. Annual failure rates ranged from 0.16 to 2.83 percent for amalgam restorations and from 0.94 to 9.43 percent for composite restorations. Secondary caries was the main reason for failure in both materials. Risk of secondary caries was 3.5 times greater in the composite group. Conclusion Amalgam restorations performed better than did composite restorations. The difference in performance was accentuated in large restorations and in those with more than three surfaces involved. Clinical Implications Use of amalgam appears to be preferable to use of composites in multisurface restorations of large posterior teeth if longevity is the primary criterion in material selection.

Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

Abstract: Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation into clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator gene CFTR have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 individuals with cystic fibrosis in registries and clinics in North America and Europe. In these individuals, 159 CFTR variants had an allele frequency of l0.01%. These variants were evaluated for both clinical severity and functional consequence, with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of individuals with cystic fibrosis enabled assignment of 12 of the remaining 32 variants as neutral, whereas the other 20 variants remained of indeterminate effect. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically relevant genomic variation.

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

Abstract: BackgroundDetailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. MethodsWe report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). ResultsThe onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of...

Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression

Abstract: During progression from single cancer cells to a tumor mass and metastases, tumor cells send signals that can subvert their tissue microenvironment. These signals involve soluble molecules and various extracellular vesicles, including a particular type termed exosomes. The specific roles of exosomes secreted in the tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B regulate exocytosis of multivesicular endosomes, which lead to exosome secretion, in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in mammary carcinoma cells decreased secretion of exosomes characterized by endocytic markers, but also of matrix metalloproteinase 9, which is not associated with exosomes. Rab27a blockade resulted in decreased primary tumor growth and lung dissemination of a metastatic carcinoma (4T1), but not of a nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization of a population of neutrophil immune cells induced by Rab27a-dependent secretion of exosomes together with a specific combination of cytokines and/or metalloproteinases. Our findings offer in vivo validation of the concept that exosome secretion can exert key pathophysiologic roles during tumor formation and progression, but they also highlight the idiosyncratic character of the tumor context.