RESUMO
BACKGROUND: Somatic genetic variants may be the cause of extracranial arteriovenous malformations, but few studies have explored these genetic anomalies, and no genotype-phenotype correlations have been identified. OBJECTIVES: The aim of the study was to characterize the somatic genetic landscape of extracranial arteriovenous malformations and correlate these findings with the phenotypic characteristics of these lesions. METHODS: This study included twenty-three patients with extracranial arteriovenous malformations that were confirmed clinically and treated by surgical resection, and for whom frozen tissue samples were available. Targeted next-generation sequencing analysis of tissues was performed using a gene panel that included vascular disease-related genes and tumour-related genes. RESULTS: We identified a pathogenic variant in 18 out of 23 samples (78.3%). Pathogenic variants were mainly located in MAP2K1 (n = 7) and KRAS (n = 6), and more rarely in BRAF (n = 2) and RASA1 (n = 3). KRAS variants were significantly (P < 0.005) associated with severe extended facial arteriovenous malformations, for which relapse after surgical resection is frequently observed, while MAP2K1 variants were significantly (P < 0.005) associated with less severe, limited arteriovenous malformations located on the lips. CONCLUSIONS: Our study highlights a high prevalence of pathogenic somatic variants, predominantly in MAP2K1 and KRAS, in extracranial arteriovenous malformations. In addition, our study identifies for the first time a correlation between the genotype, clinical severity and angiographic characteristics of extracranial arteriovenous malformations. The RAS/MAPK variants identified in this study are known to be associated with malignant tumours for which targeted therapies have already been developed. Thus, identification of these somatic variants could lead to new therapeutic options to improve the management of patients with extracranial arteriovenous malformations.
Assuntos
Malformações Arteriovenosas , Proteínas Proto-Oncogênicas p21(ras) , Malformações Arteriovenosas/genética , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína p120 Ativadora de GTPase/genéticaRESUMO
OBJECTIVES: The purpose of this study was to evaluate the impact of facial skin reconstruction training videos for head and neck and maxillofacial surgery residents. MATERIAL AND METHODS: This randomized trial, conducted in France, involved residents in head and neck and maxillofacial surgery. A website was created containing facial skin reconstruction training videos. Selected residents performed facial skin flap dissections in the Paris School of Surgery. They were randomized into two groups, one receiving a standard course before the dissection, and the other a standard course plus a video of the flap ("no-video" and "video" groups). Each resident performed 4 facial flaps and was graded (blindly) during dissection. The main study endpoint was intergroup difference in grading score (out of 15). The article was written up following the SQUIRE-EDU (Standards for QUality Improvement Reporting Excellence in EDUcation) criteria. RESULTS: Eighteen residents were included. For the main endpoint, scores were significantly higher in the "video" than the "no-video" group (6 [IQR, 4: 9] vs. 10 [9: 12]; P<0.001). In addition, as secondary endpoint, "no-video" group residents requested more assistance (3 [2: 4] vs. 1 [1: 2] P<0.001). Power was lacking for any subgroup analysis according to year of residency or to the 4 flaps. CONCLUSION: Videos improved surgical residents' performance during dissections. However, these results would be difficult to transpose to real clinical conditions. They need validating in a larger study evaluating performance in real-life procedures.
Assuntos
Internato e Residência , Procedimentos de Cirurgia Plástica , Humanos , Competência Clínica , Gravação em Vídeo , FrançaRESUMO
A triple helix is formed upon binding of an oligodeoxynucleotide to the major groove of duplex DNA. A benzo[e]pyridoindole derivative (BePI) strongly stabilized this structure and showed preferential binding to a triplex rather than to a duplex. Energy transfer experiments suggest that BePI intercalates within the triple helix. Sequence-specific inhibition of transcription initiation of a specific gene by Escherichia coli RNA polymerase by a triplex-forming oligodeoxynucleotide is strongly enhanced when the triplex is stabilized by BePI. Upon irradiation with ultraviolet light, BePI induces covalent modifications of the target within the triple helix structure.
Assuntos
DNA/metabolismo , Escherichia coli/genética , Ligantes , Sequência de Bases , Carbolinas/metabolismo , DNA/genética , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Temperatura Alta , Técnicas In Vitro , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Transcrição GênicaRESUMO
Osteoma is a benign, usually asymptomatic bone tumour, frequently arising in the nose and paranasal sinuses. Surgical treatment is required when the patient becomes symptomatic or presents ophthalmological or neurological complications. Although an endoscopic approach is increasingly used, depending on the size and site of the osteoma, open surgery may be preferable and remains the standard treatment. This technical note describes a case of giant osteoma of the frontal sinus that required a bicoronal approach with reconstruction by a custom-made titanium prosthesis.
Assuntos
Prótese Ancorada no Osso , Seio Frontal/cirurgia , Osteoma/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Seio Frontal/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Osteoma/diagnóstico por imagem , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Procedimentos de Cirurgia Plástica , Cirurgia Assistida por Computador/instrumentação , Titânio , Tomografia Computadorizada por Raios XRESUMO
Telomerase is a ribonucleoprotein (RNP) particle required for the replication of telomeres. The RNA component, termed hTR, of human telomerase contains a domain structurally and functionally related to box H/ACA small nucleolar RNAs (snoRNAs). Furthermore, hTR is known to be associated with two core components of H/ACA snoRNPs, hGar1p and Dyskerin (the human counterpart of yeast Cbf5p). To assess the functional importance of the association of hTR with H/ACA snoRNP core proteins, we have attempted to express hTR in a genetically tractable system, Saccharomyces cerevisiae. Both mature non-polyadenylated and polyadenylated forms of hTR accumulate in yeast. The former is associated with all yeast H/ACA snoRNP core proteins, unlike TLC1 RNA, the endogenous RNA component of yeast telomerase. We show that the presence of the H/ACA snoRNP proteins Cbf5p, Nhp2p and Nop10p, but not Gar1p, is required for the accumulation of mature non-polyadenylated hTR in yeast, while accumulation of TLC1 RNA is not affected by the absence of any of these proteins. Our results demonstrate that yeast telomerase is unrelated to H/ACA snoRNPs. In addition, they show that the accumulation in yeast of the mature RNA component of human telomerase depends on its association with three of the four core H/ACA snoRNP proteins. It is likely that this is the case in human cells as well.
Assuntos
Hidroliases , RNA/metabolismo , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Telomerase/genética , DNA Recombinante , Proteínas Fúngicas/metabolismo , Regulação Enzimológica da Expressão Gênica , Vetores Genéticos/genética , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Poli A/genética , Ligação Proteica , RNA/genética , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMO
Aneurysmal bone cyst are commonly seen in long bone and vertebrae. There are rare in skull bones especially in the temporal bone and zygomatic arch. We report one case in a young male of 15 years old. The main symptom was swelling of the temporo mandibular region. Clinical, radiological and therapeutic aspects of the disease are discussed with regards to the literature. The diagnosis is based on good imaging and histopathological analysis. Surgical removal is the main treatment.
Assuntos
Cistos Ósseos Aneurismáticos/patologia , Osso Temporal/patologia , Zigoma/patologia , Adolescente , Biópsia , Cistos Ósseos Aneurismáticos/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Osso Temporal/cirurgia , Zigoma/cirurgiaRESUMO
We report a case of mucormycosis in a 48 year-old diabetic woman. She presented with nasosinusal ulcer accompanied by panophthalmitis in the left eye and central retinal artery occlusion in the right eye. Left eye enucleation was performed and the diagnosis of mucormycosis was made on histopathologic examination displaying fungal micro-organisms in the optic nerve and in the retina. The patient died of stress ulcer hemorrhage. Mucormycoses are rare and severe diseases affecting immunocompromised hosts, especially diabetic patients during ketoacidosis. The treatment includes surgical debridement and amphotericin B but prognosis remains severe.
Assuntos
Infecções Oculares Fúngicas/diagnóstico , Mucormicose/diagnóstico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Desbridamento , Diabetes Mellitus Tipo 1/complicações , Enucleação Ocular , Infecções Oculares Fúngicas/patologia , Infecções Oculares Fúngicas/cirurgia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Mucorales/isolamento & purificação , Mucormicose/patologia , Mucormicose/cirurgia , Nervo Óptico/microbiologia , Nervo Óptico/patologia , Retina/microbiologia , Retina/patologiaRESUMO
Exon 5 of the human aprt gene contains an oligo-purine-oligopyrimidine stretch of 17 bp (5'-CCCTCTTCTCTCTCCT-3') within the coding region. (T,C)-, (G,T)- and (G,A)-containing oligonucleotides were compared for their ability to form stable triple helices with their DNA target. (G,T) oligodeoxynucleotides, whether parallel or antiparallel, were unable to bind to this sequence. This is in contrast to (G,A) (purine) and (T,C) (pyrimidine) oligonucleotides, which bind to the duplex at near neutral pH. Binding was highly sequence specific, as unrelated competitors were unable to interfere with target recognition. A major difference between the purine and pyrimidine oligodeoxynucleotides was observed in the kinetics of binding: the (G,A) oligonucleotide binds to its target much faster than the (T,C) oligomer. With the purine oligonucleotide, complete binding was achieved in a matter of minutes at micromolar concentrations, whereas several hours were required with the pyrimidine oligomer. Thus, the general observation that triplex formation is slow with pyrimidine oligodeoxynucleotides does not hold for (G,A) oligodeoxynucleotides. Purine and pyrimidine oligodeoxynucleotides covalently linked to a psoralen group were able to induce crosslinks on the double-stranded DNA target upon UV irradiation. This study provides a detailed comparison of the different types of DNA triplexes under the same experimental conditions.
Assuntos
Adenina Fosforribosiltransferase/genética , DNA/química , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Nucleotídeos de Purina/química , Nucleotídeos de Pirimidina/química , Acridinas/química , Sequência de Bases , Pegada de DNA , Éxons , Ficusina/química , Temperatura Alta , Humanos , Substâncias Intercalantes/química , Cinética , Dados de Sequência Molecular , Desnaturação de Ácido NucleicoRESUMO
Thermodynamic and kinetic parameters for the triplex-forming reactions between a homopurine-homopyrimidine 22-base-pair duplex (sequence of the purine strand: 5'd[AAAGGAGGAGAAGAAGAAAAAA]3') and the four 22-dN third strands (22 dN: 5'd[TTTCCTCCTCTNCTTCTTTTTT]3', where N = A, C, T, or G) were determined from thermal denaturation and renaturation UV absorbance profiles. Cooling and heating curves were not superimposable and thus allowed us to determine the rate constants of association (k(on)) and dissociation (k(off)) as a function of temperature, assuming a two-state model analogous to that developed for duplex-forming reactions. Experiments were performed in 10 mM cacodylate buffer (pH 6.8) in the presence of NaCl concentrations ranging from 20 to 300 mM. Within experimental accuracy, the main results are the following: (i) The rate constants k(on) and k(off) result in linear Arrhenius plots, consistent with the prediction of two-state association and dissociation (ii) k(on) is independent of the nature of the base N located in the center of the third strand. (iii) k(on) strongly decreases when the NaCl concentration is decreased. (iv) The activation energy, E(on), is always negative and becomes more negative when the NaCl concentration is decreased. (v) k(off) is independent of NaCl concentration but depends on the base N, with its magnitude following the order C greater than G greater than A much greater than T. (vi) The activation energy, E(off), is independent of the base N. All these results are discussed in the light of a nucleation-zipping model similar to that developed for the duplex-coil transitions [Craig, M. E., Crothers, D. M., & Doty, P. (1971) J. Mol. Biol. 62, 383-401; Pörschke, D., Eigen, M. (1971) J. Mol. Biol. 62, 361-381].