Comparison of conventional ceramic laminate veneers, partial laminate veneers and direct composite resin restorations in fracture strength after aging

Objectives: The objectives of this study were to test the fracture strength in vitro of laminate veneers, partial laminate veneers and composite restorations after aging and analyze the failure mode. Methods: Forty extracted, sound human teeth were selected and divided into four groups: 1) Control group (CG); 2) Conventional Laminate Veneer (CLV); 3) Partial Laminate Veneer (PLV); 4) Direct Composite Resin (DCR). Laminate veneer preparations with incisal overlap were made in group CLV whereas only incisal preparations were made with a 1 mm bevel in group PLV and DCR. The indirect restorations were luted with a resin composite and the DCR group was restored with a direct resin composite restoration. The restored teeth were subsequently aged by thermocycling (20.000 cycles, 5-55 degrees C). Subsequently, the fracture strength was tested by a load to failure test at 135. on the incisal edge. A failure analysis was performed using light microscopy. The results were analyzed using Shapiro-Wilk and Kruska-Wallis test. Results: After thermocycling, one sample from group CLV presented a premature adhesive failure and was excluded. Three restorations from groups PLV and DCR presented small cracks but were taken to the fracture test. After aging mean fracture load + SD (N) were: Group DCR (n = 10): 385 +/- 225; Group CG (n = 10): 271 +/- 100; Group PLV (n = 10): 266 +/- 69; Group CLV (n = 9): 264 +/- 66. Fracture strength means from groups CLV and PLV did not differ statistically from each other nor from control (p = 0.05). In the group CLV the root fracture was the most occurring fracture. In groups PLV and DCR, material cohesive failures and a mix (adhesive, tooth and material cohesive) failures were most observed. Significance: This in vitro study showed for the first time that partial laminate veneers can exhibit fracture strength values similar to direct composite restorations or conventional ceramic laminate veneers. All three restorative procedures presented clinically acceptable values of fracture strength. Even though three samples from groups PLV and three from DCR presented small cracks after thermocycling, these cracks do not appear to have a negative effect on the fracture strength

Fauna y bioestratigrafía del yacimiento Aragoniense de Montejo de la Vega de la Serrezuela (Segovia)

The macro and micromammals fossils of Montejo de la Vega de la Serrezuela (Segovia, Spain) are studied. The identified taxons allow to place the new locality in the Middle Aragonian, unit MN5 of Mein (1977, 1979, 1990). The Montejo de la Vega deposit can be correlated with the Arroyo del Olivar in the Madrid basin and the Las Planas 4A, 4B, Y4C in the Calatayud-Teruel basin.Se estudian los macro y micromamíferos fósiles de Montejo de la Vega de la Serrezuela (Segovia). Los taxones identificados permiten situar esta localidad en el Aragoniense medio, unidad MN5 de Mein (1977, 1979, 1990). El yacimiento de Montejo de la Vega puede correlacionarse con el de Arroyo del Olivar en la cuenca de Madrid y con los de Las Planas 4A, 4B y 4C en la cuenca de Calatayud-Teruel

The impact of HIV infection on the presentation of lung cancer in South Africa

Background. Despite the very high background prevalence of HIV and smoking-related diseases in sub-Saharan Africa, very little is known about the presentation of lung cancer in HIV-infected individuals.Methods. We prospectively compared HIV-positive (n=44) and HIV-negative lung cancer patients (n=425) with regard to demographics, cell type, performance status and umour node metastasis staging at initial presentation.Results. HIV-positive patients were found to be younger than HIV-negative (mean 54.1 (standard deviation (SD) 8.4) years v. 60.5 (10) years, p<0.01), more likely to have squamous cell carcinoma (43.2% v. 30.1%, p=0.07) and significantly more likely to have a poor Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 (47.7% v. 29.4%, p=0.02). In the case of non-small cell-lung cancer, they were also significantly less likely to have early stage lung cancer (0% v. 10.3%, p=0.02) compared with HIV-negative patients.Conclusions. HIV-positive lung cancer patients were younger, significantly more likely to have a poor performance status at presentation and significantly less likely to have early stage lung cancer when compared with HIV-negative patients

Cardiac circRNAs Arise Mainly From Constitutive Exons Rather Than Alternatively Spliced Exons

Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their biogenesis and function is still in its infancy. It was recently shown that alternative splicing underlies the formation of circular RNAs (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which circRNAs are formed is still unclear, we hypothesized that alternative splicing, and in particular exon skipping, is a major driver of circRNA production. We performed RNA sequencing on human and mouse hearts, mapped alternative splicing events, and overlaid these with expressed circRNAs at exon-level resolution. In addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how important Rbm20-mediated alternative splicing is in the production of cardiac circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly (~90%) produced from constitutive exons and less (~10%) from alternatively spliced exons. In Rbm20 KO hearts, we identified 38 differentially expressed circRNAs of which 12 were produced from the Ttn gene. Even though Ttn appeared the most prominent target of Rbm20 for circularization, we also detected Rbm20-dependent circRNAs arising from other genes including Fan1, Stk39, Xdh, Bcl2l13, and Sorbs1. Interestingly, only Ttn circRNAs seemed to arise from Rbm20-mediated skipped exons. In conclusion, cardiac circRNAs are mostly derived from constitutive exons, suggesting that these circRNAs are generated at the expense of their linear counterpart and that circRNA production impacts the accumulation of the linear mRNA

A new key locality for the Pliocene vertebrate record of Europe : the Camp dels Ninots maar (NE Spain)

A new Pliocene Konservat-Lagerstätte in north-eastern Spain is described here for the first time. It is referred to as Camp dels Ninots. The particular geological conditions of the site, which correspond to lacustrine sedimentation in a maar, made it ideal for the preservation of fossils. At present, five large mammal skeletons in anatomical connection have been recovered: three individuals of Alephis tigneresi, one of Stephanorhinus jeanvireti and one of Tapirus arvernenis, as well as isolated remains. A minimum of five individuals of the chelonian Mauremys leprosa have been recovered, some of them in anatomical connection. The rodent Apodemus atavus, the amphibians cf. Pleurodeles sp., Lissotriton aff. helveticus and Pelophylax cf. perezi and freshwater fishes (Leuciscus ?) complete the vertebrate assemblage uncovered up to the present time. The coexistence of Stephanorhinus jeanvireti and Alephis tigneresi suggests an age of about 3.2Ma for the Camp dels Ninots, near the MN15-MN16 transition. The Camp del Ninots fossil record enables one to extend the biogeographic range of some vertebrate taxa, such as Stephanorhinus jeanvireti, Tapirus arvernensis or Mauremys leprosa to the Iberian Peninsula. Taphonomic evidences of the skeletal remains indicates minimal (if any) weathering. Deposition at the lake bottom seems to have taken place in oxygen depleted layers. In this way, Camp dels Ninots is comparable to other remarkable maar sites such as Messel, the Eocene site situated in Germany

Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling

Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes

History matters: ecometrics and integrative climate change biology

Climate change research is increasingly focusing on the dynamics among species, ecosystems and climates. Better data about the historical behaviours of these dynamics are urgently needed. Such data are already available from ecology, archaeology, palaeontology and geology, but their integration into climate change research is hampered by differences in their temporal and geographical scales. One productive way to unite data across scales is the study of functional morphological traits, which can form a common denominator for studying interactions between species and climate across taxa, across ecosystems, across space and through time—an approach we call ‘ecometrics’. The sampling methods that have become established in palaeontology to standardize over different scales can be synthesized with tools from community ecology and climate change biology to improve our understanding of the dynamics among species, ecosystems, climates and earth systems over time. Developing these approaches into an integrative climate change biology will help enrich our understanding of the changes our modern world is undergoing

Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart

The Z-disc is a crucial structure of the sarcomere and is implicated in mechanosensation/transduction. Dysregulation of Z-disc proteins often result in cardiomyopathy. We have previously shown that the Z-disc protein Cytoskeletal Heart-enriched Actin-associated Protein (CHAP) is essential for cardiac and skeletal muscle development. Furthermore, the CHAP gene has been associated with atrial fibrillation in humans. Here, we studied the misregulated expression of CHAP isoforms in heart disease. Mice that underwent transverse aortic constriction and calcineurin transgenic (Tg) mice, both models of experimental heart failure, displayed a significant increase in cardiac expression of fetal isoform CHAPb. To investigate whether increased expression of CHAPb postnatally is sufficient to induce cardiomyopathy, we generated CHAPb Tg mice under the control of the cardiac-specific αMHC promoter. CHAPb Tg mice displayed cardiac hypertrophy, interstitial fibrosis and enlargement of the left atrium at three months, which was more pronounced at the age of six months. Hypertrophy and fibrosis were confirmed by evidence of activation of the hypertrophic gene program (Nppa, Nppb, Myh7) and increased collagen expression, respectively. Connexin40 and 43 were downregulated in the left atrium, which was associated with delayed atrioventricular conduction. Tg hearts displayed both systolic and diastolic dysfunction partly caused by impaired sarcomere function evident from a reduced force generating capacity of single cardiomyocytes. This co-incided with activation of the actin signalling pathway leading to the formation of stress fibers. This study demonstrated that the fetal isoform CHAPb initiates progression towards cardiac hypertrophy, which is accompanied by delayed atrioventricular conduction and diastolic dysfunction. Moreover, CHAP may be a novel therapeutic target or candidate gene for screening in cardiomyopathies and atrial fibrillatio

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

sharma et al. define a new primary atopic disorder caused by heterozygous gain-of-function variants in STAT6. this results in severe, early-onset allergies, and is seen in 16 patients from 10 families. Anti-IL-4R & alpha; antibody and JAK inhibitor treatment were highly effective.STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. we have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. the cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). all patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and T(H)2 skewing. Precision treatment with the anti-IL-4R & alpha; antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. this study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder