Estudo da articulação temporomandibular em portadores de sindrome de Down

Orientador : Solange Maria de AlmeidaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A Síndrome de Down é decorrente de uma alteração genética, que compreende um conjunto de sinais e sintomas próprios, como alterações crânio faciais, devido a presença de um cromossomo a mais no par de n° 21, sendo também conhecida por Trissomia do 21. Dentre outras características patognomônicas, o portador da síndrome de Down apresenta maloclusão e hipotonia muscular, o que sugere investigação sobre a função da articulação temporomandibular. Assim, 50 Down sindrôminos, foram divididos em duas amostras: a primeira denominada de grupo 1, constitui a­ se por indivíduos com idade entre 12 e 14 anos e a segunda correspondente ao grupo 2, era constituída por indivíduos com idade entre 20 e 30 anos. Esta amostra foi então avaliada pelos exames anamnésico, clínico e radiográfico, quanto à presença de sinais e sintomas de disfunção temporomandibular e a manifestação desta alteração. A análise dos resultados mostrou que o portador de síndrome de Down apresenta sinais clínicos e/ou radiográficos, e sintomas de disfunção temporomandibular, estando relacionada à idade, além de existir correlação positiva entre a hipermobilidade articular geral, hiperexcursão condi lar e disfunção temporomandibular no grupo 2Abstract: Down syndrome is a genetic alteration that understands a group of signs and symptoms, as facial alterations cranium, current of the presence of one more chromosome in the pair of number 21, that is also know by trissomy of 21. Among other patognomonics characteristics, Down syndrome individuais present malocclusion and laxity joint, what suggests investigation about the function of the temporomandibular joint. 50 Down syndrome individuais were divided in two age groups: the first group denominated group 1 was constituted by individuais, with age among 12 and 14 years old and the second group (group 2) was formed by individuais between 20 and 30 years old. 80th groups were assessment by anamnesis, clinical and radiographic examinations, looking for a sign and symptoms of temporomandibular dysfunction, and to a manifestation of this alteration. The results showed that Down syndrome individuais present signs and symptoms of the temporomandibular dysfunction that are related with age, existing high correlation among the laxity joint, condyle with hyper-excursion and temporomandibular dysfunctionDoutoradoDoutor em Radiologia Odontológic

Avaliação da tecnica radiografica intrabucal mais aceita pela criança na idade pre-escolar atraves de uma escala visual analogica de faces

Orientador: Agenor Montebello FilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O presente estudo consistiu em avaliar, através de uma Escala Visual Analógica de faces, a técnica radiográfica intrabucal mais aceita pela criança na idade pré-escolar. As técnicas avaliadas foram: Bissetriz, Paralelismo e Modificada. A amostra foi composta por 72 crianças, de ambos os sexos, com idade entre 3 e 6 anos. Os resultados mostraram que a técnica da Bissetriz foi a mais aceita para a região posterior e a técnica Modificada a mais aceita para a região anteriorAbstract: Not informed.MestradoRadiologiaMestre em Ciência

Comparative Genome Analysis of the Neurexin Gene Family in Danio rerio: Insights into Their Functions and Evolution

Neurexins constitute a family of proteins originally identified as synaptic transmembrane receptors for a spider venom toxin. In mammals, the 3 known Neurexin genes present 2 alternative promoters that drive the synthesis of a long (alpha) and a short (beta) form and contain different sites of alternative splicing (AS) that can give rise to thousands of different transcripts. To date, very little is known about the significance of this variability, except for the modulation of binding to some of the Neurexin ligands. Although orthologs of Neurexins have been isolated in invertebrates, these genes have been studied mostly in mammals. With the aim of investigating their functions in lower vertebrates, we chose Danio rerio as a model because of its increasing importance in comparative biology. We have isolated 6 zebrafish homologous genes, which are highly conserved at the structural level and display a similar regulation of AS, despite about 450 Myr separating the human and zebrafish species. Our data indicate a strong selective pressure at the exonic level and on the intronic borders, in particular on the regulative intronic sequences that flank the exons subject to AS. Such a selective pressure could help conserve the regulation and consequently the function of these genes along the vertebrates evolutive tree. AS analysis during development shows that all genes are expressed and finely regulated since the earliest stages of development, but mark an increase after the 24-h stage that corresponds to the beginning of synaptogenesis. Moreover, we found that specific isoforms of a zebrafish Neurexin gene (nrxn1a) are expressed in the adult testis and in the earliest stages of development, before the beginning of zygotic transcription, indicating a potential delivery of paternal RNA to the embryo. Our analysis suggests the existence of possible new functions for Neurexins, serving as the basis for novel approaches to the functional studies of this complex neuronal protein family and more in general to the understanding of the AS mechanism in low vertebrates

Advantages and Challenges of Cardiovascular and Lymphatic Studies in Zebrafish Research

Since its introduction, the zebrafish has provided an important reference system to model and study cardiovascular development as well as lymphangiogenesis in vertebrates. A scientific workshop, held at the 2018 European Zebrafish Principal Investigators Meeting in Trento (Italy) and chaired by Massimo Santoro, focused on the most recent methods and studies on cardiac, vascular and lymphatic development. Daniela Panáková and Natascia Tiso described new molecular mechanisms and signaling pathways involved in cardiac differentiation and disease. Arndt Siekmann and Wiebke Herzog discussed novel roles for Wnt and VEGF signaling in brain angiogenesis. In addition, Brant Weinstein’s lab presented data concerning the discovery of endothelium-derived macrophage-like perivascular cells in the zebrafish brain, while Monica Beltrame’s studies refined the role of Sox transcription factors in vascular and lymphatic development. In this article, we will summarize the details of these recent discoveries in support of the overall value of the zebrafish model system not only to study normal development, but also associated disease states

SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development.

Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SoxF binding sites established a clear requirement for members of this group of transcription factors (SOX7, SOX17 and SOX18) to drive the activity of these enhancers in vivo Endogenous deletion of the notch1b enhancer led to a significant loss of arterial connections to the dorsal aorta in Notch pathway-deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for NOTCH1 and notch1b enhancer activity and for correct endogenous transcription of these genes. These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates.This work was supported by the National Health and Medical Research Council of Australia (NHMRC) (APP1107643); The Cancer Council Queensland (1107631) (M.Fran.); the Australian Research Council Discovery Project (DP140100485) and a Career Development Fellowship (APP1111169) (M.Fran.); the Ludwig Institute for Cancer Research (M.Frit., A.N., I.R., S.D.V.); the Medical Research Council (MR/J007765/1) (K.L., G.B.-G., S.D.V.); the Fondazione Cariplo (2011-0555) (M.B., B.H., M.Fran.); and the Biotechnology and Biological Sciences Research Council (BB/L020238/1) (A.N., K.L., G.B.-G., S.D.V.)

Zebrafish Numb and Numblike Are Involved in Primitive Erythrocyte Differentiation

BACKGROUND:Notch signaling is an evolutionarily conserved regulatory circuitry implicated in cell fate determination in various developmental processes including hematopoietic stem cell self-renewal and differentiation of blood lineages. Known endogenous inhibitors of Notch activity are Numb-Nb and Numblike-Nbl, which play partially redundant functions in specifying and maintaining neuronal differentiation. Nb and Nbl are expressed in most tissues including embryonic and adult hematopoietic tissues in mice and humans, suggesting possible roles for these proteins in hematopoiesis. METHODOLOGY AND PRINCIPAL FINDINGS:We employed zebrafish to investigate the possible functional role of Numb and Numblike during hematopoiesis, as this system allows a detailed analysis even in embryos with severe defects that would be lethal in other organisms. Here we describe that nb/nbl knockdown results in severe reduction or absence of embryonic erythrocytes in zebrafish. Interestingly, nb/nbl knocked-down embryos present severe downregulation of the erythroid transcription factor gata1. This results in erythroblasts which fail to mature and undergo apoptosis. Our results indicate that Notch activity is increased in embryos injected with nb/nbl morpholino, and we show that inhibition of Notch activation can partially rescue the hematopoietic phenotype. CONCLUSIONS AND SIGNIFICANCE:Our results provide the first in vivo evidence of an involvement of Numb and Numblike in zebrafish erythroid differentiation during primitive hematopoiesis. Furthermore, we found that, at least in part, the nb/nbl morphant phenotype is due to enhanced Notch activation within hematopoietic districts, which in turn results in primitive erythroid differentiation defects

Metals impact into the Paranaguá Estuarine Complex (Brazil) during the exceptional flood of 2011

Abstract Particulate and dissolved metal concentrations were determined after the largest flood in the last 30 years on the east-west axis of the Paranaguá Estuarine Complex (PEC) and compared to the those of the dry period at two stations. Results confirmed that the flood greatly affected riverine outflows and the behavior of metals in the PEC. In particular, a sharp decrease in salinity was followed by extremely high SPM concentrations leading to a decrease in DO concentrations at both stations. For the dissolved phase, ANOSIM analysis showed a significant dissimilarity at each station between the sampled periods, whereas for the particulate phase this dissimilarity was found only for the samplings taken at the Antonina Station. KD values suggested dissolved Cu behavior was related to the presence of organic complexes and dissolved Mn had sediment resuspension of redox sediments and or/pore water injection as sources. Metal concentrations were lower than in polluted estuaries, though high enrichment factors found after the flood pointed to the influence of anthropogenic sources. In conclusion, the flood's influence was more evident at the Antonina Station, due to its location in the upper estuary, whereas in Paranaguá a high SPM content with low metal concentration was found, following the common pattern generally found in other marine systems subject to heavy rainfall events

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation