Publications by authors named "Andreas Moritz"

198 Publications

Impact of Implant Surface Material and Microscale Roughness on the Initial Attachment and Proliferation of Primary Human Gingival Fibroblasts.

Biology (Basel) 2021 Apr 22;10(5). Epub 2021 Apr 22.

Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

Due to the rising demand for zirconia (Zr) based implant systems, it is important to understand the impact of Zr and titanium (Ti) implants and particularly their topography on soft tissue healing. As human gingival fibroblasts (hGFs) are the predominant cells in peri-implant soft tissue, we focused on examining the effect of implant material and surface roughness on hGFs' initial attachment, growth and the expression of proteins involved in the focal adhesion. hGFs isolated from eight healthy donors were cultured on the following surfaces: smooth titanium machined surface (TiM), smooth zirconia machined surface (ZrM), moderately rough titanium surface (SLA), or moderately rough zirconia surface (ZLA) for up to 14 days. The initial attachment of hGFs was evaluated by scanning electron microscopy. Cell proliferation/viability was assessed by cell counting kit 8. Focal adhesion and cytoskeleton were visualized by a focal adhesion staining kit. The gene expression of focal adhesion kinase (FAK), α-smooth muscle actin (α-SMA), and integrin subunits ITG-β1, ITG-β4, ITG-α4, ITG-α5, ITG-α6, was evaluated by qPCR. Cell proliferation/viability was slightly decreased by moderately rough surfaces, whereas no effect of surface material was observed. Cell morphology was strikingly different between differently treated surfaces: on machined surfaces, cells had elongated morphology and were attached along the grooves, whereas on moderately rough surfaces, cells were randomly attached. Surface roughness had a more pronounced effect on the gene expression compared to the surface material. The expression of FAK, α-SMA, ITG-β4, ITG-α5, and ITG-α6 was enhanced by moderately rough surfaces compared to smooth surfaces. Within the limitations of this in vitro study, it can be concluded that the behavior of primary hGFs is primarily affected by surface structure, whereas no apparent advantage of Zr over Ti could be observed.
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http://dx.doi.org/10.3390/biology10050356DOI Listing
April 2021

Comparison of Glidescope Core, C-MAC Miller and conventional Miller laryngoscope for difficult airway management by anesthetists with limited and extensive experience in a simulated Pierre Robin sequence: A randomized crossover manikin study.

PLoS One 2021 22;16(4):e0250369. Epub 2021 Apr 22.

Department of Anesthesiology, Faculty of Medicine, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Background: Video laryngoscopy is an effective tool in the management of difficult pediatric airway. However, evidence to guide the choice of the most appropriate video laryngoscope (VL) for airway management in pediatric patients with Pierre Robin syndrome (PRS) is insufficient. Therefore, the aim of this study was to compare the efficacy of the Glidescope® Core™ with a hyperangulated blade, the C-MAC® with a nonangulated Miller blade (C-MAC® Miller) and a conventional Miller laryngoscope when used by anesthetists with limited and extensive experience in simulated Pierre Robin sequence.

Methods: Forty-three anesthetists with limited experience and forty-three anesthetists with extensive experience participated in our randomized crossover manikin trial. Each performed endotracheal intubation with the Glidescope® Core™ with a hyperangulated blade, the C-MAC® with a Miller blade and the conventional Miller laryngoscope. "Time to intubate" was the primary endpoint. Secondary endpoints were "time to vocal cords", "time to ventilate", overall success rate, number of intubation attempts and optimization maneuvers, Cormack-Lehane score, severity of dental trauma and subjective impressions.

Results: Both hyperangulated and nonangulated VLs provided superior intubation conditions. The Glidescope® Core™ enabled the best glottic view, caused the least dental trauma and significantly decreased the "time to vocal cords". However, the failure rate of intubation was 14% with the Glidescope® Core™, 4.7% with the Miller laryngoscope and only 2.3% with the C-MAC® Miller when used by anesthetists with extensive previous experience. In addition, the "time to intubate", the "time to ventilate" and the number of optimization maneuvers were significantly increased using the Glidescope® Core™. In the hands of anesthetists with limited previous experience, the failure rate was 11.6% with the Glidescope® Core™ and 7% with the Miller laryngoscope. Using the C-MAC® Miller, the overall success rate increased to 100%. No differences in the "time to intubate" or "time to ventilate" were observed.

Conclusions: The nonangulated C-MAC® Miller facilitated correct placement of the endotracheal tube and showed the highest overall success rate. Our results therefore suggest that the C-MAC® Miller could be beneficial and may contribute to increased safety in the airway management of infants with PRS when used by anesthetists with limited and extensive experience.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250369PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062059PMC
April 2021

What influence do vets have on vaccination decision of dog owners? Results of an online survey.

Vet Rec 2021 Apr 19:e297. Epub 2021 Apr 19.

Small Animal Clinic - Internal Medicine, Department of Veterinary Clinical Sciences, Justus-Liebig-University, Giessen, Germany.

Background: This study was performed to analyse the influence of veterinary advice as well as other sources of information on vaccination decision of dog owners.

Methods: A total of 1480 dog owners participated in this exclusively online conducted survey. Mean comparisons and correlation analyses were performed to check bivariate relationships between general data from the dogs, the dog owners, the vaccination decision making and risk/benefit analyses.

Results: The results confirm that veterinarians are the most important source of information on vaccination for dog owners. Nevertheless, the World Wide Web including social media has also to be taken into consideration as a strongly influencing factor. Additionally, the availability of serious information about vaccinations on the internet and on social media has to be reconsidered in general by the veterinarian professional sector.

Conclusions: Veterinarians should be aware of their significant influence on the owner's decision about vaccination and use this knowledge in a targeted way to achieve a high vaccination rate in order to ensure effective herd immunity. Communication strategies for veterinarians to improve information transfer to dog owners are required.
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http://dx.doi.org/10.1002/vetr.297DOI Listing
April 2021

Short-term results of the combined application of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and erbium-doped yttrium aluminum garnet (Er:YAG) laser in the treatment of periodontal disease: a randomized controlled trial.

Clin Oral Investig 2021 Apr 4. Epub 2021 Apr 4.

Division of Conservative Dentistry and Periodontology, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.

Objectives: Nd:YAG and Er:YAG lasers have been previously used as an adjunct in periodontal therapy. The aim of this single-blinded randomized controlled clinical trial was to evaluate the efficacy of a combined application of Nd:YAG and Er:YAG laser irradiation in periodontal treatment.

Materials And Methods: Twenty-two patients with at least one site of ≥ 6 mm periodontal probing depth (PPD) after mechanical debridement with curettes and sonic instruments at periodontal reevaluation were included in the study. Patients were randomly allocated at a 1:1 ratio to either a combined Nd:YAG/Er:YAG laser therapy (test group) or a "turned off" laser therapy (control group). The Nd:YAG laser was used for periodontal pocket deepithelialization and to stabilize the resulting blood clot. The Er:YAG laser was primarily used for root surface modification. PPD (mm), clinical attachment level (CAL, mm), and bleeding on probing (BOP, +/-) at the site of laser treatment were evaluated at baseline and 2 months after treatment.

Results: The mean improvements from baseline to 2-month follow-up for PPD were significantly better in the laser group (2.05 ± 0.82 mm) compared to the control group (0.64 ± 0.90 mm; p = 0.001). Likewise, the gain in CAL was significantly better in the laser group (1.50 ± 1.10 mm) than in the control group (0.55 ± 1.01mm; p = 0.046).

Conclusions: The combined application of Nd:YAG and Er:YAG laser irradiation as an adjunct to conventional non-surgical therapy showed a significant beneficial effect on periodontal treatment results.

Clinical Relevance: Combined Nd:YAG and Er:YAG laser irradiation could be a useful procedure additionally to conventional non-surgical periodontal therapy to improve periodontal treatment results.

Clinical Trial Registration: ISRCTN registry #ISRCTN32132076.
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http://dx.doi.org/10.1007/s00784-021-03911-xDOI Listing
April 2021

Platelet Activation Is Not Always Associated With Platelet-Related Plasma microRNA Abundance - Results From a Randomized Controlled Trial of Periodontal Patients.

Front Physiol 2021 1;12:613515. Epub 2021 Mar 1.

Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.

Platelets are involved in a variety of diseases, making their adequate functional assessment is essential. However, due to their easily activatable nature this has some methodological pitfalls. Therefore, the availability of stable, easily measurable surrogate markers would be beneficial. In this regard, some evidence suggests that certain microRNAs (miRNAs) circulating in plasma might be useful. We aimed to corroborate their suitability by analyzing plasma samples obtained in a randomized controlled trial, which assessed the effects of periodontal treatment on platelet function. We hypothesized that miRNA levels mirror changes of platelet activation and -function. Both platelet function and miRNA abundance were quantified using state-of-the-art flow cytometry and qPCR methods. The following miRNAs were quantified: 223-3p, 150-5p, 197-3p, 23a-3p, 126-3p, 24-3p, 21-5p, 27b-3p, 33a-5p, 320a, 191-5p, 28-3p, 451a, 29b-3p, and 1-3p. However, periodontal treatment did not affect the abundance of any investigated miRNAs to a relevant extent. Platelet activation and reactivity indices did neither correlate with any tested miRNA at baseline, nor after the treatment period. In addition, there was no evidence that investigated miRNAs were released by platelets, as suggested previously. In conclusion, our data suggest that in patients suffering from periodontal disease the investigated miRNAs are unlikely to be suitable biomarkers for platelet function. Our data aim to raise awareness that previously determined platelet activation dependent circulating miRNAs are not suitable as platelet biomarkers in all cohorts.
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http://dx.doi.org/10.3389/fphys.2021.613515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957016PMC
March 2021

Effects of Er:YAG laser irradiation of different titanium surfaces on osteoblast response.

J Mater Sci Mater Med 2021 Mar 6;32(3):22. Epub 2021 Mar 6.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

The aim of this in vitro study was to evaluate the effects of erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation on titanium surface topography and the proliferation and differentiation of osteoblasts using standard clinical treatment settings. Er:YAG laser irradiation at two levels ((1): 160 mJ, pulse at 20 Hz; (2): 80 mJ, pulse at 20 Hz) was applied to moderately rough and smooth titanium disks before MG-63 osteoblast-like cells were cultured on these surfaces. Titanium surface and cell morphology were observed by scanning electron microscopy. Cell proliferation/viability was measured by CCK-8 test. Gene expression of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and collagen type 1 was measured by qPCR, and OPG and OC protein production was determined by enzyme-linked immunosorbent assay. Treatment with Er:YAG laser at 160 mJ/20 Hz markedly caused heat-induced fusion of titanium and cell condensation on moderately rough surfaces, but not in smooth surfaces. MG-63 proliferation/viability decreased after 5 days in moderately rough surfaces. The expression of ALP, OC, OPG, and collagen type 1 was unaffected by laser treatment at 160 mJ/20. Laser irradiation at 80 mJ/20 Hz enhanced RANKL gene expression after 5 days in moderately rough surfaces. Study results suggest that Er:YAG laser irradiation at clinically relevant setting has no essential effect on osteogenic gene and protein expression of osteoblasts. However, surface structure, cell attachment, and proliferation are influenced by both treatment protocols, which implies that caution should be taken in the clinical treatment of peri-implant diseases when Er:YAG laser is used.
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http://dx.doi.org/10.1007/s10856-021-06493-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936964PMC
March 2021

Evaluation of reticulocyte hemoglobin content (RETIC-HGB) for the diagnosis of iron-limited erythropoiesis in cats.

Vet Clin Pathol 2020 Dec;49(4):557-566

Small Animal Clinic, Internal Medicine, Justus-Liebig-University, Giessen, Germany.

Background: Decreased reticulocyte hemoglobin content (CHr) (Siemens ADVIA 2120) reflects iron-limited erythropoiesis (ILE). RETIC-HGB (IDEXX ProCyte Dx) is a novel marker of ILE for veterinary use.

Objectives: We aimed to evaluate reference intervals (RIs) and the utility of RETIC-HGB and CHr in the diagnosis of feline ILE.

Materials And Methods: RIs were established in 59 healthy cats. Intra-assay coefficients of variation (CVs) and correlations between RETIC-HGB and CHr were assessed. Two hundred and seventy-five cats were classified as having ILE or not based on low plasma iron or low transferrin saturation along with anemia and/or altered RBC indices. CHr, RETIC-HGB, and serum amyloid A (SAA) were compared between the groups. The sensitivity and specificity of RETIC-HGB and CHr to diagnose ILE were analyzed to determine the RI lower limits.

Results: RIs for RETIC-HGB and CHr were 12.5-18.0 and 14.0-19.9 pg, respectively. The CV was 3% for both variables. RETIC-HGB and CHr were moderately correlated (r = 0.59) with a bias of -1.2 picograms (pgs). Twenty of the 275 cats were classified as having ILE. Compared with non-ILE cats, ILE cats had significantly lower median RETIC-HGB (14.3 vs 15.2 pg, P = .0046) and mean CHr (14.7 vs 16.5 pg, P < .0001) values and significantly increased median SAA (44.6 vs 2.3 µg/dl, P < .0001) values. Using the lower RI limits resulted in a low sensitivity and relatively high specificity to diagnose ILE in cats.

Conclusions: ILE was characterized by decreased CHr and RETIC-HGB; however, sensitivity was low. The moderate correlation between RETIC-HGB and CHr is likely due to species differences and different methodology.
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http://dx.doi.org/10.1111/vcp.12925DOI Listing
December 2020

Effect of vitamin D on the osteogenic differentiation of human periodontal ligament stromal cells under inflammatory conditions.

J Periodontal Res 2021 Feb 5. Epub 2021 Feb 5.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Objectives: Vitamin D is known to activate osteogenic differentiation of human periodontal ligament stromal cells (hPDLSCs). Recently, inflammatory stimuli were shown to inhibit the transcriptional activity of hPDLSCs, but their effect on vitamin D -induced osteogenic differentiation is not known. The present study aimed to investigate whether the effects of 1,25-dihydroxvitamin D (1,25(OH) D ) and 25-hydroxvitamin D (25(OH)D ) on the osteogenic differentiation of hPDLSCs are also altered under inflammatory conditions. Furthermore, the expression of osteogenesis-related factors by hPDLSCs under osteogenic conditions was assessed in the presence of inflammatory stimuli.

Materials And Methods: Primary hPDLSCs of six donors were cultured in osteogenic induction medium containing either 1,25(OH) D (0-10 nM) or 25(OH)D (0-100 nM) in the presence and absence of Porphyromonas gingivalis lipopolysaccharide (LPS) or Pam3CSK4 for 7, 14 and 21 days. Osteogenic differentiation of hPDLSCs was evaluated by analysis of mineralization as assessed by Alizarin Red S staining and gene expression levels of osteogenesis-related factors osteocalcin, osteopontin and runt-related transcription factor 2 (RUNX2) were analysed with qPCR.

Results: Treatment with 1,25(OH) D significantly enhanced the osteogenic differentiation of hPDLSCs and their expression of osteocalcin and osteopontin. The 1,25(OH) D -triggered expression of osteogenesis-related factors was significantly lower in the presence of Pam3CSK4, but not P. gingivalis LPS. None of the inflammatory stimuli had significant effects on the 1,25(OH) D -induced osteogenic differentiation. 25(OH)D neither affected gene expression levels nor osteogenic differentiation of hPDLSCs cultured in osteogenic induction medium.

Conclusion: The results of this study indicate that inflammatory stimuli also diminish the 1,25(OH) D -induced expression of osteogenesis-related factors in hPDLSCs under osteogenic conditions, while having no effect on the osteogenic differentiation.
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http://dx.doi.org/10.1111/jre.12858DOI Listing
February 2021

Optimizing the fitting-surface preparation of zirconia restorations for bonding to dentin.

Dent Mater 2021 03 13;37(3):464-476. Epub 2021 Jan 13.

University Clinic of Dentistry, Medical University of Vienna, Austria. Electronic address:

Objectives: The aim of this study was to identify the relative strengths and weaknesses of different interfaces within the multilayer structure of a zirconia crown restoration when applying different surface pretreatments. These include the influence on shear strengths of different air abrasion protocols, glaze-on techniques, zirconia primers and self-adhesive cements for either the complex structure: zirconia / self adhesive resin composite cement (RCC) / bovine dentin substrate (part 1) or the RCC / zirconia substrate (part 2).

Methods: In Part 1, zirconia discs, pretreated by either glaze-on techniques or air abrasion using Rocatec™ Soft, were bonded to bovine dentin substrates with different self-adhesive RCCs. In Part 2, steel-cylinders were bonded to zirconia cuboid substrates, pretreated by either different protocols for air-abrasion or a glaze-on-technique, with different self-adhesive RCCs. Shear bond strengths (SBS) were measured for all interfacial combinations.

Results: In part 1, application of air abrasion using Rocatec™ Soft significantly increased the SBS of zirconia to dentin compared to control specimens without pretreatment, while glaze-on techniques did not increase the SBS. Pretreatment of zirconia surfaces with two primers (either Clearfil Ceramic Primer, or Monobond S) showed significantly higher SBS than the controls. Cementations with RelyX Unicem 2 Automix showed significantly higher SBS than with MaxCem Elite. In Part 2, all air abrasion protocols increased the SBS, but there was no significant difference between these protocols. Again the glaze-on technique did not increase SBS. A significant difference between the two RCCs was again observed. When zirconia substrates were air abraded, regardless of which protocol was applied, the highest SBS were obtained by Calibra with P&B active followed by Panavia with or without Clearfil Ceramic Primer Plus. Calibra applied without P&B active exhibited the lowest SBS.

Significance: Pretreatment of zirconia substrates using air abrasion and/or ceramic primers increased the SBS of the zirconia cement interface. For all tested glaze-on treatments, in our experimental setting no effect was observed.
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http://dx.doi.org/10.1016/j.dental.2020.12.001DOI Listing
March 2021

Anti-apoptotic effects of human gingival mesenchymal stromal cells on polymorphonuclear leucocytes.

Oral Dis 2021 Jan 1. Epub 2021 Jan 1.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Objectives: Polymorphonuclear leucocytes (PMNs) constitute the first line of host defence and are crucial in maintaining periodontal health. Their survival and function are modulated by mesenchymal stromal cells (MSCs) from different origin. Gingival MSCs (GMSCs) play an important role in maintaining oral health and in the initial inflammatory response. The present study aimed to investigate the effects of GMSCs on PMNs apoptosis and reactive oxygen species (ROS) production.

Methods: PMNs were either directly incubated with untreated, interleukin (IL)-1β- or tumour necrosis factor (TNF)-α-treated GMSCs or stimulated with their conditioned media. Resulting ROS production was evaluated by dichlorofluorescin diacetate staining, whereas PMNs apoptosis was assessed by Annexin V staining, followed by flow cytometry analysis.

Results: While conditioned media of untreated and TNF-α-treated GMSCs did not affect apoptosis of PMNs, it was significantly delayed by conditioned media of GMSCs treated with IL-1β. In direct co-culture, GMSCs exerted anti-apoptotic effects on PMNs independently of the previous stimulation. However, the strongest impact was observed by IL-1β-treated GMSCs. ROS production of PMNs was not influenced by GMSCs or their conditioned media.

Conclusion: This study demonstrates for the first time the immunomodulatory properties of GMSCs towards PMNs, revealing that IL-1β enhances anti-apoptotic effects of GMSCs.
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http://dx.doi.org/10.1111/odi.13768DOI Listing
January 2021

Assessment of platelet biology in equine patients with systemic inflammatory response syndrome.

J Vet Diagn Invest 2021 Mar 22;33(2):300-307. Epub 2020 Dec 22.

Equine Clinic, Internal Medicine, Department of Veterinary Clinical Science, Justus Liebig University, Giessen, Germany.

In addition to maintaining hemostasis, platelets have an important role in modulating innate and adaptive immune responses. A low platelet count has been found to be a negative prognostic factor for survival in humans and horses with critical illnesses, such as sepsis or systemic inflammatory response syndrome (SIRS). Decreased platelet aggregation, caused by in vivo activation, has been found in human patients with severe sepsis. In our prospective controlled study, we assessed platelet biology in blood samples from 20 equine SIRS cases and 120 healthy control horses. Platelet variables such as platelet count, large platelet count, clumps, plateletcrit, mean platelet volume, and mean platelet component concentration were analyzed by laser flow cytometry (Advia 2120) from KEDTA blood and from citrate blood. Hirudin blood samples were analyzed by impedance aggregometry (Multiplate analyzer; Roche) for platelet aggregation, including spontaneous aggregation and aggregation by 4 different agonists: adenosine diphosphate (ADPtest), ADP + prostaglandin E1 (ADPtestHS), arachidonic acid (ASPItest), and collagen (COLtest). SIRS cases had significantly lower platelet counts in KEDTA blood ( < 0.0001) compared to control horses. There were no significant differences in aggregation values between SIRS cases and controls. Non-surviving SIRS horses did not have statistically significant lower platelet counts or lower aggregation values for COLtest, ADPtest, or ADPtestHS compared to surviving SIRS horses, although 5 non-survivors were thrombocytopenic.
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http://dx.doi.org/10.1177/1040638720983791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944423PMC
March 2021

Effect of Multi-Phosphonate Coating of Titanium Surfaces on Osteogenic Potential.

Materials (Basel) 2020 Dec 17;13(24). Epub 2020 Dec 17.

Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

The aim of this study was to evaluate the impact of a novel multi-phosphonate (MP) coating strategy of dental implant surfaces on the expression of osteogenesis-related factors in vitro. MG-63 human osteoblast-like cells, bone marrow mesenchymal stem cells (BM-MSCs), and human periodontal ligament stem cells (hPDLSCs) were cultured separately on titanium disks with and without MP coating. Cell attachment was visualized by focal adhesion and actin cytoskeleton staining. The proliferation and gene expression of the markers related to osteogenesis and bone turnover were measured after 48 and 120 h of cell culture. Actin cytoskeleton assembly and focal adhesion were similar between test surfaces within each cell type but differed from those on tissue culture plastic (TCP). The proliferation of MG-63 cells and PDLSCs was comparable on all surfaces, while BM-MSCs showed an increase on tissue culture plastic (TCP) versus titanium. The gene expression of osteoprotegerin and receptor activator of nuclear factor-kappa B ligand was higher in MG-63 cells grown on MP-coated surfaces. At the same time, osteocalcin was decreased compared to the other surfaces. Collagen type I gene expression after 120 h was significantly lower in hPDLSCs cultivated on MP-coated surfaces. Within the limitations of this study, MP coating on titanium surfaces might have a slight beneficial effect on bone turnover in vitro.
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http://dx.doi.org/10.3390/ma13245777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766650PMC
December 2020

Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells.

Cells 2020 12 16;9(12). Epub 2020 Dec 16.

Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria.

Transplanted mesenchymal stem/stromal cells (MSCs) are a promising and innovative approach in regenerative medicine. Their regenerative potential is partly based upon their immunomodulatory activities. One of the most investigated immunomediators in MSCs, such as in periodontal ligament-derived MSCs (hPDLSCs), is indoleamine-2,3-dioxygenase-1 (IDO-1) which is upregulated by inflammatory stimuli, like cytokines. However, there are no data concerning continuing IDO-1 expression in hPDLSCs after the removal of inflammatory stimuli, such as cytokines and toll-like receptor (TLR) agonist-2 and TLR-3. Hence, primary hPDLSCs were stimulated with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, TLR-2 agonist Pam3CSK4 or TLR-3 agonist Poly I/C. IDO-1 gene and protein expression and its enzymatic activity were measured up to five days after removing any stimuli. IL-1β- and TNF-α-induced IDO-1 expression and enzymatic activity decreased in a time-dependent manner after cessation of stimulation. IFN-γ caused a long-lasting effect on IDO-1 up to five days after removing IFN-γ. Both, TLR-2 and TLR-3 agonists induced a significant increase in IDO-1 gene expression, but only TLR-3 agonist induced significantly higher IDO-1 protein expression and enzymatic activity in conditioned media (CM). IDO-1 activity of Poly I/C- and Pam3CSK4-treated hPDLSCs was higher at one day after removal of stimuli than immediately after stimulation and declined to basal levels after five days. Among all tested stimuli, only IFN-γ was able to induce long-lasting IDO-1 expression and activity in hPDLSCs. The high plasticity of IDO-1 expression and its enzymatic activity in hPDLSCs due to the variable cytokine and virulence factor milieu and the temporal-dependent responsiveness of hPDLSCs may cause a highly dynamic potential of hPDLSCs to modulate immune responses in periodontal tissues.
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http://dx.doi.org/10.3390/cells9122696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765527PMC
December 2020

Analytical performance and method comparison of a quantitative point-of-care immunoassay for measurement of bile acids in cats and dogs.

J Vet Diagn Invest 2021 Jan 28;33(1):35-46. Epub 2020 Oct 28.

Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig-University, Giessen, Germany.

Point-of-care analyzers (POCAs) for quantitative assessment of bile acids (BAs) are scarce in veterinary medicine. We evaluated the Fuji Dri-Chem Immuno AU10V analyzer and v-BA test kit (Fujifilm) for detection of feline and canine total serum BA concentration. Results were compared with a 5th-generation assay as reference method and a 3rd-generation assay, both run on a bench-top analyzer. Analytical performance was assessed at 3 different concentration ranges, and with interferences. For method comparison, samples of 60 healthy and diseased cats and 64 dogs were included. Linearity was demonstrated for a BA concentration up to 130 µmol/L in cats ( = 0.99) and 110 µmol/L in dogs ( = 0.99). The analyzer showed high precision near the lower limit of quantification of 2 µmol/L reported by the manufacturer. Intra- and inter-assay coefficients of variation were < 5% for both species and all concentrations. Interferences were observed for bilirubin (800 mg/L) and lipid (4 g/L). There was excellent correlation with the reference method for feline ( = 0.98) and canine samples ( = 0.97), with proportional biases of 6.7% and -1.3%, respectively. However, a large bias (44.1%) was noted when the POCA was compared to the 3rd-generation assay. Total observed error was less than total allowable error at the 3 concentrations. The POCA reliably detected feline and canine BA in clinically relevant concentrations.
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http://dx.doi.org/10.1177/1040638720968784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756073PMC
January 2021

The impact of 3D-printed LAY-FOMM 40 and LAY-FOMM 60 on L929 cells and human oral fibroblasts.

Clin Oral Investig 2021 Apr 20;25(4):1869-1877. Epub 2020 Sep 20.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.

Objectives: LAY-FOMM is a promising material for FDA-approved Fused Deposition Modeling (FDM) applications in drug delivery. Here we investigated the impact on oral cells.

Materials And Methods: We evaluated the impact of 3D-printed LAY-FOMM 40, LAY-FOMM 60, and biocompatible polylactic acid (PLA) on the activity of murine L929 cells, gingival fibroblasts (GF), and periodontal ligament fibroblasts (PDLF) using indirect (samples on cells), direct monolayer culture models (cells on samples), and direct spheroid cultures with resazurin-based toxicity assay, confirmed by MTT and Live-dead staining. The surface topography was evaluated with scanning electron microscopy.

Results: The materials LAY-FOMM 40 and LAY-FOMM 60 led to a reduction in resazurin conversion in L929 cells, GF, and PDLF, higher than the impact of PLA in indirect and direct culture models. Fewer vital cells were found in the presence of LAY-FOMM 40 and 60 than PLA, in the staining in both models. In the direct model, LAY-FOMM 40 and PLA showed less impact on viability in the resazurin-based toxicity assay than in the indirect model. Spheroid microtissues showed a reduction of cell activity of GF and PDLF with LAY-FOMM 40 and 60.

Conclusion: Overall, we found that LAY-FOMM 40 and LAY-FOMM 60 can reduce the activity of L292 and oral cells. Based on the results from the PLA samples, the direct model seems more reliable than the indirect model.

Clinical Relevance: A material modification is desired in terms of biocompatibility as it can mask the effect of drugs and interfere with the function of the 3D-printed device.
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http://dx.doi.org/10.1007/s00784-020-03491-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966624PMC
April 2021

Effectiveness of a 655-nm InGaAsP diode laser to detect subgingival calculus in patients with periodontal disease.

J Periodontol 2021 04 2;92(4):547-552. Epub 2020 Sep 2.

Austrian Cluster for Tissue Regeneration, Vienna, Austria.

Background: Previous in vitro studies have proven laser fluorescence measurement using a 655-nm Indium Gallium Arsenide Phosphide (InGaAsP) based diode laser radiation to be a useful tool to detect subgingival calculus. The aim of this prospective study was to evaluate the 655-nm InGaAsP diode laser in detecting subgingival calculus in patients with periodontal disease compared with photographic assessment during periodontal surgery.

Methods: Twelve patients (six women, six men) aged between 21 and 75 years with periodontitis scheduled for periodontal surgery were included in this prospective study. All laser fluorescence measurements were made before periodontal surgery. Intraoperatively a mucoperiostal flap was performed, subgingival calculus was visualized, and photographic images were taken. The presence of calculus was recorded for each evaluated site.

Results: A total of 115 tooth surface sites of 32 teeth from the 12 patients were evaluated before (laser) and during surgery (image). Compared with image evaluation the laser assessment showed a sensitivity of 0.70 (CI 0.53 to CI 0.83) and a specificity of 0.97 (CI 0.85 to CI 0.99). The overall probability to correctly detect subgingival calculus with the laser (accuracy) was 0.82 (CI 0.74 to CI 0.88).

Conclusions: The 655-nm diode laser was able to detect subgingival calculus. Hence, the 655 nm diode laser may be used as an additional tool for calculus detection in non-surgical periodontal therapy.
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http://dx.doi.org/10.1002/JPER.19-0663DOI Listing
April 2021

Comparison of Glidescope® Go™, King Vision™, Dahlhausen VL, I‑View™ and Macintosh laryngoscope use during difficult airway management simulation by experienced and inexperienced emergency medical staff: A randomized crossover manikin study.

PLoS One 2020 30;15(7):e0236474. Epub 2020 Jul 30.

Department of Anesthesiology, University Hospital Erlangen, Faculty of Medicine, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Background: In pre-hospital emergency care, video laryngoscopes (VLs) with disposable blades are preferably used due to hygienic reasons. However, there is limited existing data on the use of VLs with disposable blades by emergency medical staff. Therefore, the aim of this study was to compare the efficacy of four different VLs with disposable blades and the conventional standard Macintosh laryngoscope, when used by anesthetists with extensive previous experience and paramedics with little previous experience in endotracheal intubation (ETI) in a simulated difficult airway.

Methods: Fifty-eight anesthetists and fifty-four paramedics participated in our randomized crossover manikin trial. Each performed ETI with the new Glidescope® Go™, the Dahlhausen VL, the King Vision™, the I-View™ and the Macintosh laryngoscope. "Time to intubate" was the primary endpoint. Secondary endpoints were "time to vocal cords", "time to ventilate", overall success rate, number of intubation attempts and optimization maneuvers, Cormack-Lehane score, severity of dental compression and subjective impressions.

Results: The Glidescope® Go™, the Dahlhausen VL and the King Vision™ provided superior intubation conditions in both groups without affecting the number of intubation attempts or the time required for successful intubation. When used by anesthetists with extensive experience in ETI, the use of VLs did not affect the overall success rate. In the hands of paramedics with little previous experience in ETI, the failure rate with the Macintosh laryngoscope (14.8%) decreased to 3.7% using the Glidescope® Go™ and the Dahlhausen VL. Despite the advantages of hyperangulated video laryngoscopes, the I-View™ performed worst.

Conclusions: VLs with hyperangulated blades facilitated ETI in both groups and decreased the failure rate by an absolute 11.1% when used by paramedics with little previous experience in ETI. Our results therefore suggest that hyperangulated VLs could be beneficial and might be the method of choice in comparable settings, especially for emergency medical staff with less experience in ETI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236474PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392330PMC
September 2020

Response of Human Mesenchymal Stromal Cells from Periodontal Tissue to LPS Depends on the Purity but Not on the LPS Source.

Mediators Inflamm 2020 2;2020:8704896. Epub 2020 Jul 2.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Human periodontal ligament stromal cells (hPDLSCs) and gingival mesenchymal stromal cells (hGMSCs) are resident mesenchymal stromal cells (MSCs) of the periodontal tissue. The lipopolysaccharide (LPS) from is structurally distinct from that of other Gram-negative bacteria, and earlier studies linked this structural difference to a distinct virulence activity and the ability to activate toll-like receptor 2 (TLR-2), besides TLR-4 as commonly occurring upon LPS challenge. Later studies, in contrast, argue that TLR-2 activation by LPS is due to lipoprotein contamination. In the present study, we aimed to define the influence of structure versus purity of LPS on the immune response of hPDLSCs and hGMSCs. Cells were stimulated with commercially available "standard" LPS, "ultrapure" LPS, or "ultrapure" LPS, and the expression of interleukin- (IL-) 8, IL-6, monocyte chemoattractant protein- (MCP-) 1, TLR-2, and TLR-4 was evaluated. The contribution of TLR-4 to the LPS-induced response was assessed using the specific TLR-4 inhibitor TAK-242. "Standard" LPS induced significantly higher IL-8, IL-6, and MCP-1 production compared to the "ultrapure" LPS preparations, with no significant difference detectable for "ultrapure" LPS from and . By using TAK-242, the response of hPDLSCs and hGMSCs to "ultrapure" LPS preparations was effectively inhibited to the levels comparable to those of nonstimulated controls. In contrast, high levels of response to "standard" LPS were observed, even in the presence of TAK-242. Our data show that the response of MSCs from periodontal tissue to LPS depends more on the purity of the LPS preparation than on the LPS source. Even a small amount of contaminating lipoproteins can drastically enhance the hPDLSCs' and hGMSCs; responsiveness to LPS, which might also contribute to the progression of periodontal disease.
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http://dx.doi.org/10.1155/2020/8704896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352132PMC
July 2020

Transcriptional activity of vitamin D receptor in human periodontal ligament cells is diminished under inflammatory conditions.

J Periodontol 2021 01 21;92(1):137-148. Epub 2020 Jun 21.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Background: Although vitamin D deficiency is considered as a risk factor for periodontitis, supplementation during periodontal treatment has not been shown to be beneficial to date. Human periodontal ligament cells (hPDLCs) are regulated by vitamin D and play a fundamental role in periodontal tissue homeostasis and inflammatory response in periodontitis. The aim of this study is to investigate possible alterations of the vitamin D activity in hPDLCs under inflammatory conditions.

Methods: Cells isolated from six different donors were treated with either 1,25(OH) D (0 to 10 nM) or 25(OH)D (0 to 100 nM) in the presence and absence of ultrapure or standard Porphyromonas gingivalis lipopolysaccharide (PgLPS), Pam3CSK4, or interferon-γ for 48 hours. Additionally, nuclear factor (NF)-κB inhibition was performed with BAY 11-7082. The bioactivity of vitamin D in hPDLCs was assessed based on the gene expression levels of vitamin D receptor (VDR)-regulated genes osteocalcin and osteopontin. Additionally, VDR and CYP27B1 expression levels were measured.

Results: The vitamin D -induced increase of osteocalcin and osteopontin expression was significantly decreased in the presence of standard PgLPS and Pam3CSK4, which was not observed by ultrapure PgLPS. Interferon-y had diverse effects on the response of hPDLCs to vitamin D metabolites. NF-kB inhibition abolished the effects of standard PgLPS and Pam3CSK4. Standard PgLPS and Pam3CSK4 increased VDR expression in the presence of vitamin D . CYP27B1 expression was not affected by vitamin D and inflammatory conditions.

Conclusions: This study indicates that the transcriptional activity of VDR is diminished under inflammatory conditions, which might mitigate the effectiveness of vitamin D supplementation during periodontal treatment.
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http://dx.doi.org/10.1002/JPER.19-0541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891446PMC
January 2021

Effect of interdental brush design on plaque during nonsurgical periodontal therapy.

Clin Oral Investig 2021 Jan 27;25(1):87-94. Epub 2020 May 27.

Department of Periodontology, Medical Faculty, Sigmund Freud University Vienna, Freudplatz 3, 1020, Vienna, Austria.

Objective: The aim of this randomized controlled trial was to evaluate the interproximal cleaning efficacy of waist-shaped compared with straight soft interdental brushes in patients undergoing nonsurgical periodontal therapy.

Materials And Methods: Ten patients diagnosed with periodontitis stage II or III were scheduled for nonsurgical periodontal therapy. Baseline plaque control record (PCR), modified approximal plaque index (API), papillary bleeding index (PBI), probing pocket depth (PPD), and bleeding on probing (BOP) were evaluated. Four interdental spaces of equal sizes were determined, and baseline plaque indices (PI) were assessed on eight surfaces of the respective adjacent teeth, resulting in 640 measuring positions. Interdental brushes with a straight or waist-shaped design were randomly allocated to the right or left side, and patients received oral hygiene instructions. Follow-up measurements including PCR, API, PBI, and site-specific PI were performed during initial nonsurgical periodontal therapy sessions and reevaluation which was undertaken 8 weeks afterwards.

Results: PCR, API, and PBI decreased significantly compared with baseline at each time point (p < 0.001). PPD (waist-shaped, baseline 4 mm (range, 2-9 mm) vs. reevaluation 3 mm (range, 1-6 mm); p < 0.001; straight, baseline 4 mm (range, 2-10) vs. reevaluation 3 mm (range, 1-6) mm; p < 0.001) and BOP (p = 0.008) showed significant reduction in both groups. Sub-analysis of site-specific areas including line angles and interproximal areas revealed no significant reduction of plaque during the observation period between both brush designs. No difference between straight and waist-shaped brushes regarding PPD or BOP decrease was found.

Conclusion: The efficacy of both interdental brush designs concerning plaque control in patients undergoing nonsurgical periodontal therapy was similar.

Clinical Relevance: The use of interdental brushes is essential for biofilm removal in patients during initial periodontal therapy, regardless of brush design.

Clinical Trial Registration: ISRCTNregistry (#ISRCTN24498365), http://www.isrctn.com/ISRCTN24498365.
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http://dx.doi.org/10.1007/s00784-020-03337-xDOI Listing
January 2021

Extremely high canine C-reactive protein concentrations > 100 mg/l - prevalence, etiology and prognostic significance.

BMC Vet Res 2020 May 20;16(1):147. Epub 2020 May 20.

Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig-University Giessen, Frankfurter Str. 114, 35392, Giessen, Germany.

Background: In human medicine, extremely high CRP (C-reactive protein) concentrations > 100 mg/l are indicators of bacterial infection and the need of antibiotic treatment. Similar decision limits for septic pneumonia are recommended for dogs but have not yet been evaluated for other organ systems. The aim of the retrospective study was to investigate the prevalence and evaluate dogs with CRP concentrations > 100 mg/l regarding the underlying etiology, the affected organ system and the prognostic significance.

Results: Prevalence of CRP > 100 mg/l was investigated in dogs presented between 2014 and 2015 and was 12%. For evaluation of etiology and organ systems, dogs with CRP > 100 mg/l presented between 2014 and 2016 were enrolled. Dogs were classified into 4 main disease categories, i.e. inflammatory, neoplastic, tissue damage or "diverse". Diseases were assigned to the affected organ system. If an organ classification was not possible, dogs were classified as "multiple". 147 dogs with CRP 101-368 mg/l were included and classified into disease categories: 86/147 (59%) with inflammatory etiology (among these, 23/86 non-infectious, 44/86 infectious (33/44 bacterial), 19/86 inflammation non-classifiable), 31/147 (21%) tissue damage, 17/147 (12%) neoplastic (all malignant) and 13/147 (9%) diverse diseases. The affected organ systems included 57/147 (39%) multiple, 30/147 (20%) trauma, 21/147 (14%) gastrointestinal tract, 10/147 (7%) musculoskeletal system, 8/147 (5%) respiratory tract, 7/147 (5%) urinary/reproductive tract, 6/147 (4%) skin/subcutis/ear, 6/147 (4%) central/peripheral nervous system and 2/147 (1%) heart. The disease group (p = 0.081) or organ system (p = 0.17) did not have an impact on CRP. Based on CRP, a detection of bacterial infection was not possible. The prognostic significance was investigated by determining the 3-months survival and hospitalization rate in a subgroup with known outcome. The 3-months survival rate was 46/73 (63%) while the majority 66/73 (90%) of patients was hospitalized.

Conclusions: CRP concentrations > 100 mg/l are occasionally seen in a clinic population. They indicate a severe systemic disease of various etiologies with guarded prognosis. Extremely high CRP concentrations do not allow a conclusion of the underlying etiology or an identification of bacterial inflammation.
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http://dx.doi.org/10.1186/s12917-020-02367-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237877PMC
May 2020

Cytokines Differently Define the Immunomodulation of Mesenchymal Stem Cells from the Periodontal Ligament.

Cells 2020 05 14;9(5). Epub 2020 May 14.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.

Human periodontal ligament stem cells (hPDLSCs) play an important role in periodontal tissue homeostasis and regeneration. The function of these cells depends largely on their immunomodulatory ability, which is reciprocally regulated by immune cells via cytokines, particularly interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Different cytokines activate distinct signaling pathways and might differently affect immunomodulatory activities of hPDLSCs. This study directly compared the effect of IFN-γ, TNF-α, or IL-1β treated primary hPDLSCs on allogenic CD4 T lymphocyte proliferation and apoptosis in an indirect co-culture model. The effects of IFN-γ, TNF-α, and IL-1β on the expression of specific immunomodulatory factors such as intoleamine-2,3-dioxygenase-1 (IDO-1), prostaglandin E (PGE), and programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) in hPDLSCs were compared. The contribution of different immunomodulatory mediators to the immunomodulatory effects of hPDLSCs in the indirect co-culture experiments was assessed using specific inhibitors. Proliferation of CD4 T lymphocytes was inhibited by hPDLSCs, and this effect was strongly enhanced by IFN-γ and IL-1β but not by TNF-α. Apoptosis of CD4 T lymphocytes was decreased by hPDLSCs per se. This effect was counteracted by IFN-γ or IL-1β. Additionally, IFN-γ, TNF-α, and IL-1β differently regulated all investigated immunomediators in hPDLSCs. Pharmacological inhibition of immunomediators showed that their contribution in regulating CD4 T lymphocytes depends on the cytokine milieu. Our data indicate that inflammatory cytokines activate specific immunomodulatory mechanisms in hPDLSCs and the expression of particular immunomodulatory factors, which underlies a complex reciprocal interaction between hPDLSCs and CD4 T lymphocytes.
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http://dx.doi.org/10.3390/cells9051222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290931PMC
May 2020

Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

BMC Oral Health 2020 04 25;20(1):125. Epub 2020 Apr 25.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, A-1090, Vienna, Austria.

Background: Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. The purpose of this systematic review and meta-analysis was to evaluate the effect of bisphosphonate coated implant surfaces on alkaline phosphatase activity in osteoblasts.

Methods: In vitro studies that assessed alkaline phosphatase activity in osteoblasts following cell culture on bisphosphonate coated titanium surfaces were searched in electronic databases PubMed/MEDLINE, Scopus and ISI Web of Science. Animal studies and clinical trials were excluded. The literature search was restricted to articles written in English and published up to August 2019. Publication bias was assessed by the construction of funnel plots.

Results: Eleven studies met the inclusion criteria. Meta-analysis showed that coating of titanium surfaces with bisphosphonates increases alkaline phosphatase activity in osteoblasts after 3 days (n = 1), 7 (n = 7), 14 (n = 6) and 21 (n = 3) days. (7 days beta coefficient = 1.363, p-value = 0.001; 14 days beta coefficient = 1.325, p-value < 0.001; 21 days beta coefficient = 1.152, p-value = 0.159).

Conclusions: The meta-analysis suggests that bisphosphonate coatings of titanium implant surfaces may have beneficial effects on osteogenic behaviour of osteoblasts grown on titanium surfaces in vitro. Further studies are required to assess to which extent bisphosphonates coating might improve osseointegration in clinical situations.
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http://dx.doi.org/10.1186/s12903-020-01089-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183598PMC
April 2020

Pleiotropic effects of vitamin D on CD4 T lymphocytes mediated by human periodontal ligament cells and inflammatory environment.

J Clin Periodontol 2020 06 13;47(6):689-701. Epub 2020 Apr 13.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Aims: Both, vitamin D and human periodontal ligament cells (hPDLCs) possess immunosuppressive properties, but their combined effect on immune cells has never been investigated. Here, we analysed the impact of vitamin D on the immunosuppressive properties of hPDLCs towards CD4 T lymphocytes.

Material And Methods: Allogenic CD4 T lymphocytes were activated by phytohemagglutinin either in monoculture or co-culture with hPDLCs, in the presence or absence of IFN-γ and 1,25(OH) D . After 5 days, CD4 T-lymphocyte proliferation, CD4 CD25 FoxP3 regulatory T lymphocytes (T ) proportion and IL-10, TGF-β1 and IL-17A production were analysed.

Results: In monoculture, 1,25(OH) D suppressed CD4 T-lymphocyte proliferation, increased the percentage of CD4 FoxP3 CD25 FoxP3 T and enhanced IL-10 and TGF-β1 production. In the presence of IFN-γ treated hPDLCs, 1,25(OH) D significantly increased CD4 T-lymphocyte proliferation and decreased the percentage of CD4 CD25 FoxP3 T . IL-10 and IL-17A expression was significantly diminished by 1,25(OH) D , whereas TGF-β1 was slightly increased. The effects of 1,25(OH) D in co-culture were reversed by inhibition of indoleamine-2,3-dioxygenase-1, prostaglandin-endoperoxide synthase and programmed cell death 1 ligand 1. 1,25(OH) D also suppressed the expression of these proteins in hPDLCs.

Conclusion: Effects of vitamin D on CD4 T lymphocyte are modified by hPDLCs depending on the microenvironment.
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http://dx.doi.org/10.1111/jcpe.13283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318673PMC
June 2020

Nociception testing during fixed-wing ambulance flights. An interventional pilot study on the effects of flight-related environmental changes on the nociception of healthy volunteers.

PLoS One 2020 24;15(2):e0217530. Epub 2020 Feb 24.

Department of Anesthesiology, University Hospital Erlangen, Erlangen, Germany.

Background: The effects of environmental changes on the somato-sensory system during long-distance air ambulance flights need to be further investigated. Changes in nociceptive capacity are conceivable in light of previous studies performed under related environmental settings. We used standardized somato-sensory testing to investigate nociception in healthy volunteers during air-ambulance flights.

Methods: Twenty-five healthy individuals were submitted to a test compilation analogous to the quantitative sensory testing battery-performed during actual air-ambulance flights. Measurements were paired around the major changes of external factors during take-off/climb and descent/landing. Bland-Altman-Plots were calculated to identify possible systemic effects.

Results: Bland-Altman-analyses suggest that the thresholds of stimulus detection and pain as well as above-threshold pain along critical waypoints of travel are not subject to systemic effects but instead demonstrate random variations.

Conclusions: We provide a novel description of a real-life experimental setup and demonstrate the general feasibility of performing somato-sensory testing during ambulance flights. No systematic effects on the nociception of healthy individuals were apparent from our data. Our findings open up the possibility of future investigations into potential effects of ambulance flights on patients suffering acute or chronic pain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039504PMC
April 2020

The Influence of Pro-Inflammatory Factors on Sclerostin and Dickkopf-1 Production in Human Dental Pulp Cells Under Hypoxic Conditions.

Front Bioeng Biotechnol 2019 17;7:430. Epub 2019 Dec 17.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Sclerostin (Sost) and dickkopf (Dkk)-1 are inhibitors of the Wnt signaling pathway that plays a role in regenerative processes. Hypoxia-based strategies are used for regenerative approaches, but the influence of hypoxia on Sost and Dkk-1 production in a pro-inflammatory environment is unclear. The aim of this study was to assess if pro-inflammatory molecules have an influence on Sost and Dkk-1 production in dental pulp cells (DPC) under normoxia and hypoxia. Human DPC were treated with interleukin (IL)-1β, tumor necrosis factor (TNF)α or transforming growth factor (TGF)β, with L-mimosine (L-MIM) or hypoxia or a combination. Sost and Dkk-1 mRNA and protein levels were measured with qPCR and western blot, respectively. TNFα, TGFβ, L-MIM, or combined treatment did not modulate Sost and Dkk-1. IL-1β downregulated Sost at the mRNA level. Hypoxia alone and together with inflammatory markers downregulated Dkk-1 at the mRNA level. Sost and Dkk-1 protein production was below the detection limit. In conclusion, there is a differential effect of hypoxia and IL-1β on the mRNA production of Sost and Dkk-1. Pro-inflammatory molecules do not further modulate the effects of L-MIM or hypoxia on Sost and Dkk-1 production in DPC.
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http://dx.doi.org/10.3389/fbioe.2019.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927906PMC
December 2019

1,25(OH)D Differently Affects Immunomodulatory Activities of Mesenchymal Stem Cells Depending on the Presence of TNF-α, IL-1β and IFN-γ.

J Clin Med 2019 Dec 14;8(12). Epub 2019 Dec 14.

Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, 1090 Wien, Austria.

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)D on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)D on the proliferation of allogenic CD4 T lymphocyte or on the functional status of primary CD68 macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)D on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)D increased or decreased CD4 T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)D and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)D significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)D influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.
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http://dx.doi.org/10.3390/jcm8122211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947512PMC
December 2019

The efficacy of ultrasonic and PIPS (photon-induced acoustic streaming) irrigation to remove artificially placed dentine debris plugs out of an artificial and natural root model.

Lasers Med Sci 2020 Apr 28;35(3):719-728. Epub 2019 Nov 28.

Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.

The aim was to validate an artificial resin 'root canal wall groove model' (RCWGM) mimicking the situation of natural roots with a groove of identical dimensions on debris removal out of these grooves, and to evaluate Erbium 'laser-activated irrigation' (LAI) with two conical tips at PIPS (photon-induced photoacoustic streaming) settings, with different activation times and different root canal positions on debris removal out of the grooves. A split RCWGM was used (resin blocks and roots of maxillary canines) with a canal size 40/0.06. The grooves in the apical third were filled with stained dentinal debris. Seventeen irrigation protocols (n = 20) were used: syringe-needle irrigation (3× 20 s), manual dynamic activation (1× 60 s), ultrasonically activated irrigation (UAI) with 25/25 Irrisafe (3× 20 s) and LAI (2940 nm Er:YAG) with X-Pulse or PIPS tips at PIPS settings (20 mJ, 50 μs, 20 Hz) and with the fibre (IN) or (OUT) the canal: IN during 1× 20 s, and OUT during 1× 20 s, 2× 20 s, 3× 20 s, 30 s, 2× 30 s and 1× 60 s. The quantity of remaining dentine debris in the groove was evaluated on a numerical scale. Statistical analysis was performed by means of proportional odds logistic regression, equivalence testing and Wald tests. The level of significance was set at 0.05. Resin models and the RCWGM with natural teeth can be called equivalent (log odds ratio 0.185). There were mostly no statistically significant differences for debris removal between UAI and LAI (p > 0.05) and between LAI with PIPS and X-Pulse (p > 0.05). Although not statistically different, the numbers of completely cleaned grooves were higher with LAI than with UAI for a 1-min activation, confirming findings from other studies. There is no difference in cleaning efficacy between X-Pulse and PIPS tips at PIPS settings.
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http://dx.doi.org/10.1007/s10103-019-02912-3DOI Listing
April 2020

Workload and influencing factors in non-emergency medical transfers: a multiple linear regression analysis of a cross-sectional questionnaire study.

BMC Health Serv Res 2019 Nov 7;19(1):812. Epub 2019 Nov 7.

Faculty of Medicine, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

Background: Human workload is a key factor for system performance, but data on emergency medical services (EMS) are scarce. We investigated paramedics' workload and the influencing factors for non-emergency medical transfers. These missions make up a major part of EMS activities in Germany and are growing steadily in number.

Methods: Paramedics rated missions retrospectively through an online questionnaire. We used the NASA-Task Load Index (TLX) to quantify workload and asked about a variety of medical and procedural aspects for each mission. Teamwork was assessed by the Weller teamwork measurement tool (TMT). With a multiple linear regression model, we identified a set of factors leading to relevant increases or decreases in workload.

Results: A total of 194 non-emergency missions were analysed. Global workload was rated low (Mean = 27/100). In summary, 42.8% of missions were rated with a TLX under 20/100. TLX subscales revealed low task demands but a very positive self-perception of performance (Mean = 15/100). Teamwork gained high ratings (Mean TMT = 5.8/7), and good teamwork led to decreases in workload. Aggression events originating from patients and bystanders occurred frequently (n = 25, 12.9%) and increased workload significantly. Other factors affecting workload were the patient's body weight and the transfer of patients with transmittable pathogens.

Conclusion: The workload during non-emergency medical transfers was low to very low, but performance perception was very positive, and no indicators of task underload were found. We identified several factors that led to workload increases. Future measures should attempt to better train paramedics for aggression incidents, to explore the usefulness of further technical aids in the transfer of obese patients and to reconsider standard operating procedures for missions with transmittable pathogens.
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http://dx.doi.org/10.1186/s12913-019-4638-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836439PMC
November 2019

Haemostatic, fibrinolytic and inflammatory profiles in West Highland white terriers with canine idiopathic pulmonary fibrosis and controls.

BMC Vet Res 2019 Oct 29;15(1):379. Epub 2019 Oct 29.

Department of Veterinary Clinical Sciences, FARAH, University of Liege, Avenue de Cureghem 3, 4000, Liège, Belgium.

Background: Canine idiopathic pulmonary fibrosis (CIPF) is a progressive interstitial lung disease mainly affecting old West Highland white terriers (WHWTs). The aetiology of CIPF is currently unknown and pathogenesis poorly understood. A genetic basis is strongly suspected based on the breed predisposition. CIPF shares clinical and pathological features with human IPF. In human IPF, coagulation disorders favouring a local and systemic pro-thrombotic state have been demonstrated in association with disease severity and outcome. The aim of this study was to compare the systemic haemostatic, fibrinolytic and inflammatory profiles of WHWTs affected with CIPF with breed-matched controls (CTRLs). Additionally, data collected in both groups were interpreted with regard to the reference intervals (when available) to assess possible pro-thrombotic features of the WHWT breed that may be related to CIPF predisposition. A total of 14 WHWTs affected with CIPF and 20 CTRLs were included.

Results: WHWTs affected with CIPF had prolonged activated partial thromboplastine time in comparison with CTRLs (12.2 ± 0.9 s vs. 11.5 ± 0.7 s, P = 0.028), whereas results obtained in both groups were all within reference ranges. There was no significant difference between groups for the other factors assessed including plasmatic concentrations of fibrinogen, D-dimers concentration, antithrombin III activity, protein S and protein C activities, anti-factor Xa activity, activated protein C ratio, serum C-reactive protein concentration, and rotational thromboelastometry indices. Platelet count and plasmatic fibrinogen concentration were found to be above the upper limit of the reference range in almost half of the WHWTs included, independently of the disease status.

Conclusions: Results of this study provide no clear evidence of an altered systemic haemostatic, fibrinolytic or inflammatory state in WHWTs affected with CIPF compared with CTRLs. The higher platelet counts and fibrinogen concentrations found in the WHWT breed may serve as predisposing factors for CIPF or simply reflect biological variation in this breed.
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http://dx.doi.org/10.1186/s12917-019-2134-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819526PMC
October 2019