Fully guided implant surgery using Magnetic Resonance Imaging – An in vitro study on accuracy in human mandibles

Objectives: The objective of this in vitro study was to assess the accuracy of fully guided implant placement following virtual implant planning based on MRI. Material and methods: Sixteen human cadaver hemimandibles with single missing teeth (n = 3), partially edentulous (n = 6) and edentulous situations (n = 7) were imaged using MRI. MRI and optical scans obtained with an intraoral scanner, were imported into an implant planning software. Virtual prosthetic and implant planning were performed regarding hard- and soft-tissue anatomy. Drill guides were manufactured, and fully guided implant placement was performed. Buccal and lingual bone and implant nerve distance were measured by three examiners in preoperative MRI and postoperative CBCT. The implant position was assessed using a software for deviation of implant positions displayed in CBCT and optical scans, respectively. Results: MRI displayed relevant structures for implant planning such as cortical and cancellous bone, inferior alveolar nerve and neighboring teeth. Implant planning, CAD/CAM of drill guides and guided implant placement were performed. Deviations between planned and actual implant positions in postoperative CBCT and optical scans were 1.34 mm (SD 0.84 mm) and 1.03 mm (SD 0.46 mm) at implant shoulder; 1.41 mm (SD 0.88 mm) and 1.28 mm (SD 0.52 mm) at implant apex, and 4.84° (SD 3.18°) and 4.21° (SD 2.01°). Measurements in preoperative MRI and postoperative CBCT confirmed the compliance with minimum distances of implants to anatomical structures. Conclusions: Relevant anatomical structures for imaging diagnostics in implant dentistry are displayed with MRI. The accuracy of MRI-based fully guided implant placement in vitro is comparable to the workflow using CBCT

Widespread decline in Central European plant diversity across six decades

Abstract Based on plant occurrence data covering all parts of Germany, we investigated changes in the distribution of 2136 plant species between 1960 and 2017. We analyzed 29 million occurrence records over an area of ~350,000 km 2 on a 5 × 5 km grid using temporal and spatiotemporal models and accounting for sampling bias. Since the 1960s, more than 70% of investigated plant species showed declines in nationwide occurrence. Archaeophytes (species introduced before 1492) most strongly declined but also native plant species experienced severe declines. In contrast, neophytes (species introduced after 1492) increased in their nationwide occurrence but not homogeneously throughout the country. Our analysis suggests that the strongest declines in native species already happened in the 1960s–1980s, a time frame in which often few data exist. Increases in neophytic species were strongest in the 1990s and 2010s. Overall, the increase in neophytes did not compensate for the loss of other species, resulting in a decrease in mean grid cell species richness of −1.9% per decade. The decline in plant biodiversity is a widespread phenomenon occurring in different habitats and geographic regions. It is likely that this decline has major repercussions on ecosystem functioning and overall biodiversity, potentially with cascading effects across trophic levels. The approach used in this study is transferable to other large‐scale trend analyses using heterogeneous occurrence data

Engineered hybrid spider silk particles as delivery system for peptide vaccines

The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable

Proton and Li-Ion Permeation through Graphene with Eight-Atom-Ring Defects

Defect-free graphene is impermeable to gases and liquids but highly permeable to thermal protons. Atomic-scale defects such as vacancies, grain boundaries and Stone-Wales defects are predicted to enhance graphene's proton permeability and may even allow small ions through, whereas larger species such as gas molecules should remain blocked. These expectations have so far remained untested in experiment. Here we show that atomically thin carbon films with a high density of atomic-scale defects continue blocking all molecular transport, but their proton permeability becomes ~1,000 times higher than that of defect-free graphene. Lithium ions can also permeate through such disordered graphene. The enhanced proton and ion permeability is attributed to a high density of 8-carbon-atom rings. The latter pose approximately twice lower energy barriers for incoming protons compared to the 6-atom rings of graphene and a relatively low barrier of ~0.6 eV for Li ions. Our findings suggest that disordered graphene could be of interest as membranes and protective barriers in various Li-ion and hydrogen technologies

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

ABSTRACT Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood

Complex c-di-GMP Signaling Networks Mediate Transition between Virulence Properties and Biofilm Formation in Salmonella enterica Serovar Typhimurium

Upon Salmonella enterica serovar Typhimurium infection of the gut, an early line of defense is the gastrointestinal epithelium which senses the pathogen and intrusion along the epithelial barrier is one of the first events towards disease. Recently, we showed that high intracellular amounts of the secondary messenger c-di-GMP in S. typhimurium inhibited invasion and abolished induction of a pro-inflammatory immune response in the colonic epithelial cell line HT-29 suggesting regulation of transition between biofilm formation and virulence by c-di-GMP in the intestine. Here we show that highly complex c-di-GMP signaling networks consisting of distinct groups of c-di-GMP synthesizing and degrading proteins modulate the virulence phenotypes invasion, IL-8 production and in vivo colonization in the streptomycin-treated mouse model implying a spatial and timely modulation of virulence properties in S. typhimurium by c-di-GMP signaling. Inhibition of the invasion and IL-8 induction phenotype by c-di-GMP (partially) requires the major biofilm activator CsgD and/or BcsA, the synthase for the extracellular matrix component cellulose. Inhibition of the invasion phenotype is associated with inhibition of secretion of the type three secretion system effector protein SipA, which requires c-di-GMP metabolizing proteins, but not their catalytic activity. Our findings show that c-di-GMP signaling is at least equally important in the regulation of Salmonella-host interaction as in the regulation of biofilm formation at ambient temperature

The UGT1A6_19_GG genotype is a breast cancer risk factor

Validation of an association between the UGT1A6_19_T>G (rs6759892) polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA). An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS), Germany (BBCC), and Sweden (SASBAC). The pooled analysis included 7418 cases and 8720 controls from all six studies. Participants were of European descent. Genotyping was done by MALDI-TOF MS and statistical analysis was performed by logistic regression adjusted for age and study. The increased overall breast cancer risk for women with the UGT1A6_19_GG genotype which was observed in the pilot study was confirmed in the set of four independent study collections (OR 1.13, 95% CI 1.05–1.22; p = 0.001). The pooled study showed a similar effect (OR 1.09, 95% CI 1.04–1.14; p = 0.001). The risk effect on the basis of allele frequencies was highly significant, the pooled analysis showed an OR of 1.11 (95% CI 1.06–1.16; p = 5.8 × 10−6). We confirmed the association of UGT1A6_19_GG with increased overall breast cancer risk and conclude that our result from a well powered multi-stage study adds a novel candidate to the panel of validated breast cancer susceptibility loci