Zum initialen Einfluss weiter Mundöffnungen bei zahnärztlicher Behandlung auf das Bewegungsmuster der Mandibula

Die vorliegende klinisch-experimentelle Studie befasst sich mit dem möglichen Einfluss von länger andauernder weiter Mundöffnung, wie sie typischerweise bei Zahnbehandlungen auftritt, auf das individuelle Bewegungsmuster des Unterkiefers. Es nahmen 15 männliche zahn- und kaufunktionsgesunde Probanden im Alter von 19 bis 26 Jahre an der Studie teil. Insgesamt wurden für jeden Probanden 2 Messzyklen ausgewertet. Der erste Messzyklus erfolgte im entspannten Zustand unmittelbar vor der ca. 30 Minuten andauernden weiten Mundöffnung statt. Der zweite Messzyklus wurde sofort im Anschluss and die Mundöffnungsphase erfasst. Folgende Bewegungen wurden mit Hilfe des computergestützten JMA-Registriersystem der Fa. Zebris dokumentiert: Schließbewegung aus weiter Mundöffnung, zahngeführte exkursive Protrusion und Laterotrusion nach rechts und links. Mögliche Abweichungen der Bewegungen wurden in der Horizontal- und Sagittalebene mit den Winkeln α (für Adduktion), β (Links-Laterotrusion), γ (Rechts-Laterotrusion) und δ (Protrusion) bechrieben. Die Vergleich der beiden Messzyklen ergab, dass sich unter andauernder Mundöffnung: 1. der Schließwinkel α um 2,1°, 2. die Laterotrusionswinkel β um 1,7° und γ um 2.1° sowie 3. der Protrusionswinkel δ um 1,6° signifikant reduzieren. Aus den veränderten Bewegungsspuren resultiert zwangsläufig auch eine zumindest temporäre Veränderung der okklusalen Kompasse. Die Resultate von Okklusionskontrollen, welche unmittelbar im Anschluss an eine länger dauernde Zahnbehandlung durchgeführt wird, sollten daher mit Zurückhaltung interpretiert werden. Scheinbare okklusale Interferenzen könnten die Folge des durch Mundöffnung veränderten Bewegungsmusters der Mandibula sein. Dieser Umstand ist auch beim selektiven okklusalen Einschleifen sowie bei der zentrischen Kieferrelationsbestimmung und protrusiven und laterotrusiven Checkbissen zur Programmierung des Artikulators zu berücksichtigen

A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

<p>Abstract</p> <p>Background</p> <p>Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), <it>in vitro </it>cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface.</p> <p>Results</p> <p>A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 μg/cm². The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber.</p> <p>Dose-response measurements with ZnO nanoparticles (0.3-8.5 μg/cm²) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 μg/cm²ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels.</p> <p>Conclusion</p> <p>The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.</p

Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence

Ampattu BJ, Hagmann L, Liang C, et al. Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics. 2017;18(1): 282.Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain alpha 522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p) ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis

Effects of Genetic Variants in ADCY5, GIPR, GCKR and VPS13C on Early Impairment of Glucose and Insulin Metabolism in Children

OBJECTIVE: Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children. RESEARCH DESIGN AND METHODS: We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage. RESULTS: The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity. CONCLUSIONS: Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Zum initialen Einfluss weiter Mundöffnungen bei zahnärztlicher Behandlung auf das Bewegungsmuster der Mandibula

Die vorliegende klinisch-experimentelle Studie befasst sich mit dem möglichen Einfluss von länger andauernder weiter Mundöffnung, wie sie typischerweise bei Zahnbehandlungen auftritt, auf das individuelle Bewegungsmuster des Unterkiefers. Es nahmen 15 männliche zahn- und kaufunktionsgesunde Probanden im Alter von 19 bis 26 Jahre an der Studie teil. Insgesamt wurden für jeden Probanden 2 Messzyklen ausgewertet. Der erste Messzyklus erfolgte im entspannten Zustand unmittelbar vor der ca. 30 Minuten andauernden weiten Mundöffnung statt. Der zweite Messzyklus wurde sofort im Anschluss and die Mundöffnungsphase erfasst. Folgende Bewegungen wurden mit Hilfe des computergestützten JMA-Registriersystem der Fa. Zebris dokumentiert: Schließbewegung aus weiter Mundöffnung, zahngeführte exkursive Protrusion und Laterotrusion nach rechts und links. Mögliche Abweichungen der Bewegungen wurden in der Horizontal- und Sagittalebene mit den Winkeln α (für Adduktion), β (Links-Laterotrusion), γ (Rechts-Laterotrusion) und δ (Protrusion) bechrieben. Die Vergleich der beiden Messzyklen ergab, dass sich unter andauernder Mundöffnung: 1. der Schließwinkel α um 2,1°, 2. die Laterotrusionswinkel β um 1,7° und γ um 2.1° sowie 3. der Protrusionswinkel δ um 1,6° signifikant reduzieren. Aus den veränderten Bewegungsspuren resultiert zwangsläufig auch eine zumindest temporäre Veränderung der okklusalen Kompasse. Die Resultate von Okklusionskontrollen, welche unmittelbar im Anschluss an eine länger dauernde Zahnbehandlung durchgeführt wird, sollten daher mit Zurückhaltung interpretiert werden. Scheinbare okklusale Interferenzen könnten die Folge des durch Mundöffnung veränderten Bewegungsmusters der Mandibula sein. Dieser Umstand ist auch beim selektiven okklusalen Einschleifen sowie bei der zentrischen Kieferrelationsbestimmung und protrusiven und laterotrusiven Checkbissen zur Programmierung des Artikulators zu berücksichtigen