Publications by authors named "Kathrin Becker"

84 Publications

Challenging diagnostic work-up of a massive fluid-filled structure in the cranial abdomen of a cat.

Tierarztl Prax Ausg K Kleintiere Heimtiere 2021 Oct 12. Epub 2021 Oct 12.

Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation.

A 9-year-old female, neutered European shorthair cat was presented with acute vomiting, obvious jaundice and painful enlargement of the abdomen. Icteric skin and mucous membranes in addition to severe bilirubinaemia (mainly direct bilirubin) and a large increase in liver enzyme activities were the main findings at the initial examination. Radio- and ultrasonographic evaluation revealed a massive fluid-filled structure caudal to the liver displacing abdominal organs, in particular the stomach. As this structure with a diameter of 8-10 cm occupied considerable space in the cranioventral abdomen, a detailed ultrasonographic examination of the liver and the gallbladder, and determination of the structure's association with a particular abdominal organ was initially impossible. Via ultrasound-assisted puncture under general anaesthesia 300 ml of an almost clear fluid could be aspirated. Cytological examination revealed a cyst content-like fluid with cell detritus.Further ultrasonographic and computed tomographic diagnostics followed by abdominal laparotomy finally enabled diagnosis of a cystic dilatation of the entire common bile duct and accumulation of white bile. Histopathological examination after euthanasia (requested by the owner) identified lymphoplasmacytic cholangitis and necrosis of the duodenal papilla. The massive dilatation of the common bile duct complicated its definite diagnosis by diagnostic imaging methods. It was most likely caused by a longer-standing obstruction of the bile flow by lymphoplasmacytic cholangitis with necrosis and granulation tissue formation in the area of the duodenal papilla. An interesting but initially misleading feature was the presence of white bile. The etiology of this extremely rare condition remains obscure but in the described case a manifestation of impaired hepatocyte function secondary to biliary stasis is suspected to be the cause.
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http://dx.doi.org/10.1055/a-1518-6202DOI Listing
October 2021

The Effects of Three Chlorhexidine-Based Mouthwashes on Human Osteoblast-Like SaOS-2 Cells. An In Vitro Study.

Int J Mol Sci 2021 Sep 15;22(18). Epub 2021 Sep 15.

Department of Oral Surgery, University Clinic of Düsseldorf, 40225 Düsseldorf, Germany.

Several decontamination methods for removing biofilm from implant surfaces during surgical peri-implantitis treatment have been reported, including the intraoperative usage of chlorhexidine (CHX)-based antiseptics. There is a lack of information on possible adverse effects on bone healing. The study aimed to examine the impact of three CHX-based mouthwashes on osteoblast-like cells (SaOS-2) in vitro. Cells were cultured for three days in 96-well binding plates. Each well was randomly treated for either 30, 60 or 120 s with 0.05% CHX combined with 0.05% cetylpyridinium chloride (CPC), 0.1% CHX, 0.2% CHX or sterile saline (NaCl) as control. Cell viability, cytotoxicity and apoptosis were assessed at day 0, 3 and 6. Cell viability resulted in being higher in the control group at all time points. At day 0, the CHX 0.2 group showed significantly higher cytotoxicity values compared to CHX 0.1 (30 s), CHX + CPC (30 s, 60 s and 120 s) and control (60 s and 120 s), while no significant differences were identified between CHX + CPC and both CHX 0.1 and NaCl groups. All test mouthwashes were found to induce apoptosis to a lower extent compared to control. Results indicate that 0.2% CHX presented the highest cytotoxic effect. Therefore, its intraoperative use should be carefully considered.
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http://dx.doi.org/10.3390/ijms22189986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470316PMC
September 2021

Bone remodelling patterns around orthodontic mini-implants migrating in bone: an experimental study in rat vertebrae.

Eur J Orthod 2021 Sep 3. Epub 2021 Sep 3.

Department of Orthodontics, University Clinic of Düsseldorf, Germany.

Background: Orthodontic implant migration has been clinically observed in presence of continuous loading forces. Recent studies indicate that osteocytes play a crucial role in this phenomenon.

Objectives: Aim of this study was to investigate local osteocytic gene expression, protein expression, and bone micro-structure in peri-implant regions of pressure and tension.

Material And Methods: The present work reports a complementary analysis to a previous micro-computed tomography study. Two customized mini-implants were placed in one caudal rat vertebra and connected by a nickel-titanium contraction spring generating different forces (i.e. 0, 0.5, 1.0, and 1.5 N). Either at 2 or 8 weeks, the vertebrae were harvested and utilized for 1. osteocytic gene expression using laser capture micro-dissection on frozen sections coupled with qPCR, 2. haematoxylin-eosin staining for qualitative and quantitative analyses, 3. immunofluorescence staining and analysis, and 4. bone-to-implant contact on undecalcified samples.

Results: At the two time points for all the performed analyses no significant differences were observed with respect to the applied force magnitudes and cell harvesting localization. However, descriptive histological analysis revealed remarkable bone remodelling at 2 weeks of loading. At 8 weeks the implants were osseointegrated and, especially in 1.0 and 1.5 N groups, newly formed bone presented a characteristic load bearing architecture with trabecula oriented in the direction of the loading.

Conclusions: The present study confirmed that stress-induced bone remodelling is the biological mechanism of orthodontic implant migration. Bone apposition was found at 'tension' and 'pressure' sites thus limiting implant migration over time.
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http://dx.doi.org/10.1093/ejo/cjab065DOI Listing
September 2021

Standardized assessment of bone micromorphometry around teeth following orthodontic tooth movement : A µCT split-mouth study in mice.

J Orofac Orthop 2021 Aug 3. Epub 2021 Aug 3.

Department of Orthodontics, Universitätsklinikum Düsseldorf, 40225, Düsseldorf, Germany.

Purpose: Volumetric quantitative analyses of bone micromorphometry changes following orthodontic tooth movements are hardly standardizable. The present study aimed at validating and applying a novel microcomputed tomography (CT)-based approach that enables the segmentation of teeth and definition of a standardized volume of interest (VOI) around the roots to assess local bone micromorphometry.

Methods: The jaws of 3 untreated and 14 orthodontically treated mice (protraction of the upper right molar for 11 days with 0.5 N; untreated left upper molar) were scanned with a micro-CT. The first molars and the alveolar bone were segmented, and a standardized VOI was defined around the teeth. The bone volume per total volume (BV/TV) was assessed within the VOI, and BV/TV values were compared between contralateral sites in both untreated (method validation) and treated animals (method application).

Results: The intraclass correlation coefficient of 0.99 revealed high reliability of the method. In the untreated animals, Bland-Altman analysis confirmed comparable BV/TV fractions (mean difference: -1.93, critical difference: 1.91, Wilcoxon: p = 0.03). In the orthodontically treated animals, BV/TV values were significantly lower at the test compared to the control site (test: 33.23% ± 5.74%, control: 41.33% ± 4.91%, Wilcoxon: p < 0.001).

Conclusion: Within the limits of the study, the novel approach demonstrated the applicability to evaluate bone micromorphometry around teeth subjected to orthodontic treatment.
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http://dx.doi.org/10.1007/s00056-021-00336-9DOI Listing
August 2021

Efficacy of 0.05% Chlorhexidine and 0.05% Cetylpyridinium Chloride Mouthwash to Eliminate Living Bacteria on In Situ Collected Biofilms: An In Vitro Study.

Antibiotics (Basel) 2021 Jun 17;10(6). Epub 2021 Jun 17.

Department of Oral Surgery, University of Düsseldorf, 40225 Düsseldorf, Germany.

Chlorhexidine (CHX) mouthwashes are frequently used as an adjunctive measure for the treatment of periodontitis and peri-implantitis, as well as in patients on maintenance therapy. However, their prolonged use is associated with several side effects. This study aimed at evaluating if a mouthwash with a reduced concentration of CHX combined with cetylpyridnium chloride (CPC) was as effective as a conventional CHX mouthwash in the reduction in living cells in oral biofilms attached to hydroxyapatite (HA) and micro-rough titanium (Ti) surfaces. Four healthy volunteers wore a customized acrylic appliance containing HA and Ti discs for in situ plaque accumulation. Biofilms were grown on the discs for 24 or 48 h and then randomly exposed for 60 s to: 0.05% CHX + 0.05% CPC, 0.1% CHX (positive control) or sterile saline (negative control). Viability assay and live-dead staining were performed to quantify bacterial viability and to distinguish live and dead cells, respectively. At both time points, contrary to saline, CHX, both alone and in combination with CPC, exhibited high antibacterial properties and induced a significant reduction in biofilm viability. This study demonstrates the potential of mouthwashes containing a low concentration of CHX combined with CPC as effective antibacterial agents for long-term applications with reduced undesired side effects.
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http://dx.doi.org/10.3390/antibiotics10060730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235160PMC
June 2021

COVID-19: Review of European recommendations and experts' opinion on dental care. Summary and consensus statements of group 5. The 6th EAO Consensus Conference 2021.

Clin Oral Implants Res 2021 Oct;32 Suppl 21:382-388

Faculty of Odontology, Malmo University, Malmo, Sweden.

Objectives: The present work reports the EAO workshop group 5 and consensus plenary discussions and statements based on two reviews summarising European guidelines and experts' opinion on infection control and prevention (ICP) in dentistry during the pandemic.

Material: Two manuscripts were presented at the 6th EAO Consensus Conference. The first study compared the most recent national guidelines/recommendations of European countries. The second paper was an experts' opinion-based survey on application of ICP regulation during the second wave. The outcome of COVID-19 group discussion was presented to all participants of the consensus to come to an agreement about the consensus statements and clinical recommendation.

Results: The dynamic of the pandemic had an impact on rapidly published and frequently updated national guidelines in Europe. As guidelines were not based on solid evidence, they were supplemented by experts' opinion on ICP in dentistry. The dental care should be guaranteed during the pandemic; however, in case of suspected or confirmed COVID-19 disease, the treatment should be postponed if possible. Remote triage and patient-related measures (i.e., social distancing, hand hygiene and mask wearing) were recommended to be the most efficient to reduce SARS-CoV-2 transmission. The type of personal protective equipment for dental staff should be adequate to the procedure and infection risk.

Conclusions: Adequate infection control protocols have to be followed by healthcare professionals and patients to minimise the spreading of COVID-19. We foresee the importance of continuously updating the national dental guidelines, considering the evolution of the pandemic and new scientific evidence becoming available.
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http://dx.doi.org/10.1111/clr.13780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444925PMC
October 2021

Dental care during COVID-19 pandemic: Follow-up survey of experts' opinion.

Clin Oral Implants Res 2021 Oct;32 Suppl 21:342-352

Faculty of Odontology, Malmö University, Malmö, Sweden.

Objectives: The purpose of the present survey is to give an update of European experts' opinion on infection control and prevention in dentistry during second wave of pandemic. The secondary aim was to analyze how experts' opinion changed in the light of the new scientific evidence since the first wave.

Material & Methods: An anonymous online 14-item questionnaire was sent to a total of 27 leading academic experts in Oral (and Maxillofacial) Surgery from different European countries, who had completed a previous survey in April-May 2020. The questionnaire covered the topics of dental setting safety, personal protective equipment (PPE), and patient-related measures to minimize transmission risk. Data collection took place in November-February 2020/21.

Results: 26 experts participated in the follow-up survey. The overall transmission risk in dental settings was scored significantly lower compared to the initial survey (p < .05), though the risk associated with aerosol-generating procedures (AGP) was still considered to be high. Maximum PPE was less frequently recommended for non-AGP (p < .05), whereas the majority of experts still recommended FFP2/FFP3 masks (80.8%), face shields or goggles (88.5%), gowns (61.5%), and caps (57.7%) for AGP. Most of the experts also found mouth rinse relevant (73.1%) and reported to be using it prior to treatment (76.9%). No uniform opinion was found regarding the relevance of COVID-19 testing of staff and patients.

Conclusion: With the continuation of dental care provision, transmission risk has been scored lower compared to the first wave of pandemic. However, high risk is still assumed for AGP, and maximum PPE remained advised for the respective treatments.
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http://dx.doi.org/10.1111/clr.13783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444799PMC
October 2021

Summary of European guidelines on infection control and prevention during COVID-19 pandemic.

Clin Oral Implants Res 2021 Oct;32 Suppl 21:353-381

Faculty of Odontology, Malmo University, Malmo, Sweden.

Objectives: The current COVID-19 pandemic highlighted the need for a review of guidelines on infection control and prevention to ensure safe delivery of dental care. However, it is not clear to what extent the rapidly published European guidelines reflect the current evidence and thus provide homogeneous recommendations.

Material & Methods: Guidelines from all European Union countries, Scotland, Switzerland and United Kingdom were retrieved. Information on triage, mouth rinse, personal protective equipment (PPE) for aerosol free/ generating procedures (non-AGP/AGP) and treatment of potentially infectious patients were summarized and compared with recommendations from international organizations (WHO, ECDC, CDC).

Results: All included countries (30/30) published COVID-19 guidelines in 2020. All countries recommended triage and to postpone non-urgent treatment of potentially infectious patients. Hydrogen peroxide (1%-1.5%) was the most frequently recommended antiseptic mouth rinse to reduce viral load (24/30). PPE for non-AGP treatments included mainly surgical masks (21/30) or FFP2/FFP3/N95 masks (16/30), whereas FFP2/FFP3 masks (25/30) and face shields (24/30) were recommended for AGP by the vast majority of guidelines. For high-risk/COVID positive patients, most countries recommended maximum protection and treatment in specialized dental clinics (22/30).

Conclusion: There was general agreement among recommendations for triage, mouth rinse, and PPE during AGP and treatment of potentially infectious patients. In contrast, recommendations on PPE for non-AGP treatment varied considerably among the European countries possibly due to limited scientific evidence regarding transmission risk during non-AGP treatments.
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http://dx.doi.org/10.1111/clr.13784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444665PMC
October 2021

Enteric Ganglioneuritis, a Common Feature in a Subcutaneous TBEV Murine Infection Model.

Microorganisms 2021 Apr 18;9(4). Epub 2021 Apr 18.

Department of Infectious Diseases, Institute for Parasitology, University of Veterinary Medicine, Buenteweg 17, 30559 Hanover, Germany.

Tick-borne encephalitis (TBE) is a severe neurologic disease in Europe and Asia. Disease expression ranges from asymptomatic to severe neurological clinical pictures, involving meningitis, encephalitis, meningoencephalitis and potentially fatal outcome. Humans mostly become infected with TBE virus (TBEV) by the bite of an infected tick. Gastrointestinal (GI) symptoms in humans are mainly attributed to the first viremic phase of TBEV infection with unspecific symptoms and/or resulting from severe neurological impairment of the central nervous system (CNS). We used the subcutaneous TBEV-infection of C57BL/6 mice as a model to analyze GI complications of TBE. We observed the acute distension and segmental dilation of the intestinal tract in 10 of 22 subcutaneously infected mice. Histological analysis revealed an intramural enteric ganglioneuritis in the myenteric and submucosal plexus of the small and large intestine. The numbers of infiltrating macrophages and CD3 T lymphocytes correlated with the severity of ganglioneuritis, indicating an immune-mediated pathogenesis due to TBEV-infection of the enteric plexus. Our study demonstrates that the inflammation of enteric intramural ganglia presents to be a common feature in TBEV-infected mice. Accordingly, the results of this mouse model emphasize that GI disease manifestation and consequences for long-term sequelae should not be neglected for TBEV-infections in humans and require further investigation.
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http://dx.doi.org/10.3390/microorganisms9040875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074024PMC
April 2021

Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters.

Viruses 2021 04 8;13(4). Epub 2021 Apr 8.

Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.
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http://dx.doi.org/10.3390/v13040639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069375PMC
April 2021

Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2.

Front Immunol 2021 12;12:640842. Epub 2021 Apr 12.

Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.
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http://dx.doi.org/10.3389/fimmu.2021.640842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072219PMC
May 2021

Automated tooth segmentation as an innovative tool to assess 3D-tooth movement and root resorption in rodents.

Head Face Med 2021 Feb 3;17(1). Epub 2021 Feb 3.

Department of Orthodontics, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.

Background: Orthodontic root resorptions are frequently investigated in small animals, and micro-computed tomography (μCT) enables volumetric comparison. Despite, due to overlapping histograms from dentine and bone, accurate quantification of root resorption is challenging. The present study aims at (i) validating a novel automated approach for tooth segmentation (ATS), (ii) to indicate that matching of contralateral teeth is eligible to assess orthodontic tooth movement (OTM) and root resorption (RR), (iii) and to apply the novel approach in an animal trial performing orthodontic tooth movement.

Methods: The oral apparatus of three female mice were scanned with a μCT. The first molars of each jaw and animal were segmented using ATS (test) and manually (control), and contralateral volumes were compared. Agreement in root volumes and time efficiency were assessed for method validation. In another n = 14 animals, the left first upper molar was protracted for 11 days at 0.5 N, whereas the contralateral molar served as control. Following ATS, OTM and RR were estimated.

Results: ATS was significantly more time efficient compared to the manual approach (81% faster, P < 0.01), accurate (volume differences: - 0.01 ± 0.04 mm), and contralateral roots had comparable volumes. Protracted molars had significantly lower root volumes (P = 0.03), whereas the amount of OTM failed to reveal linear association with RR (P > 0.05).

Conclusions: Within the limits of the study, it was demonstrated that the combination of ATS and registration of contralateral jaws enables measurements of OTS and associated RR in μCT scans.
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http://dx.doi.org/10.1186/s13005-020-00254-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856769PMC
February 2021

The prevalence of peri-implant disease following immediate implant placement and loading: a cross-sectional analysis after 2 to 10 years.

Int J Implant Dent 2020 Oct 19;6(1):63. Epub 2020 Oct 19.

Department of Oral Surgery and Implantology, Johann Wolfgang Goethe-University, Carolinum, Frankfurt am Main, Germany.

Background: To evaluate the prevalence of peri-implant disease after immediate implant placement and loading.

Material And Methods: This cross-sectional analysis included a total of 47 patients with 64 implants exhibiting a mean loading time of 2 to 10 years (4.23 ± 1.7 years). The surgical and prosthetic procedures were standardized in all patients. Peri-implant health and disease was assessed based on the established case definitions.

Results: The prevalence of peri-implant health, peri-implant mucositis, and peri-implantitis amounted to 38.3%, 57.5%, and 4.2% of the patients, respectively. Mucosal recession of 1 mm was present at 4 (6%) implants. No suppuration, pain, or implant failures were reported. Ordinal logistic regression revealed that reduced keratinized mucosa height was significantly associated with the diagnosis of peri-implant mucositis and peri-implantitis (OR = 0.514, P = 0.0125).

Conclusion: Immediate implant placement and loading was associated with high success rates at 2 to 10 years.
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http://dx.doi.org/10.1186/s40729-020-00259-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569077PMC
October 2020

Dental care during COVID-19 pandemic: Survey of experts' opinion.

Clin Oral Implants Res 2020 Dec 30;31(12):1253-1260. Epub 2020 Oct 30.

Faculty of Odontology, Malmo University, Malmo, Sweden.

Objectives: The current COVID-19 outbreak in conjunction with the need to provide safe dental treatments and the limited knowledge on the efficacy of protective measures has posed dentists into a challenging situation. Therefore, the present article aimed at collecting experiences and recommendations of frontline clinical experts on critical aspects of dental treatment provision during pandemic.

Material & Methods: From a total of 32 European countries, one leading academic expert in Oral and Maxillofacial Surgery or Oral Surgery per country was asked to participate in an anonymous online 10-item survey on COVID-19 covering the topics of safety of dental settings, personal protective equipment (PPE), and patient-related measures to reduce transmission risk. Data collection took place from April 12th to May 22nd, 2020.

Results: A total of 27 experts from different European countries completed the survey. The transmission risk of SARS-CoV-2 in dental settings for aerosol-generating procedures was considered high by all experts except two. For aerosol-free and aerosol-generating procedures, more than 80% of the experts recommended face protection and caps for every single treatment. For aerosol-generating procedures, additional measures (FFP2/FFP3 masks and gowns) were suggested by the vast majority of the experts. To reduce transmission risk, all experts recommended limiting aerosol-generating procedures and reducing the number of patients in waiting areas as well as hand hygiene for the patients.

Conclusion: The limitation of aerosol-generating procedures along with the usage of adequate personal protection equipment was considered to be crucial to protect dental healthcare providers and patients, thus reducing the transmission risk of COVID-19.
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http://dx.doi.org/10.1111/clr.13676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675432PMC
December 2020

29th Annual Scientific Meeting of the European Association for Osseointegration, 5-11 October 2020.

Clin Oral Implants Res 2020 10;31 Suppl 20:4-299

Universitätsklinikum Düsseldorf, Düsseldorf, Germany.

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http://dx.doi.org/10.1111/clr.13643DOI Listing
October 2020

Microstructural volumetric analysis of vertical alveolar ridge augmentation using autogenous tooth roots.

Clin Implant Dent Relat Res 2020 Oct 2;22(5):647-653. Epub 2020 Sep 2.

Department of Oral Surgery and Implantology, Johann Wolfgang Goethe-University, Carolinum, Frankfurt, Germany.

Background: To volumetrically assess the bone microstructure following vertical alveolar ridge augmentation using differently conditioned autogenous tooth roots (TR) and second-stage implant placement.

Materials And Methods: The upper premolars were bilaterally extracted in n = 4 beagle dogs and randomly assigned to either autoclavation (TR-A) or no additional treatment (TR-C). Subsequently, TR were used as block grafts for vertical alveolar ridge augmentation in both lower quadrants. At 12 weeks, titanium implants were inserted and left to heal 3 weeks. Microcomputed tomography was used to quantify bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) at vestibular (v) and oral (o) aspects along the implant and in the augmented upper half of the implant, respectively.

Results: Median BV/TV [TR-C: 51.33% (v) and 70.42% (o) vs TR-A: 44.05% (v) and 64.46% (o)], Tb.th [TR-C: 0.22 mm (v) and 0.27 mm (o) vs TR-A: 0.23 mm (v) and 0.29 mm (o)] and Tb.Sp [TR-C: 0.26 mm (v) and 0.13 mm (o) vs TR-A: 0.29 μm (v) and 0.15 mm (o)] values were comparable in both groups.

Conclusion: Both TR-C and TR-A grafts were associated with a comparable bone microstructure within the grafted area.
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http://dx.doi.org/10.1111/cid.12947DOI Listing
October 2020

TNF-α modulation via Etanercept restores bone regeneration of atrophic non-unions.

Bone 2020 12 31;141:115569. Epub 2020 Jul 31.

University Hospital BG Bergmannsheil Bochum, Germany. Electronic address:

Treatment of atrophic non-unions, especially in long bones is a challenging problem in orthopedic surgery due to the high revision and failure rate after surgical intervention. Subsequently, there is a certain need for a supportive treatment option besides surgical treatment. In our previous study we gained first insights into the dynamic processes of atrophic non-union formation and observed a prolonged inflammatory reaction with upregulated TNF-α levels and bone resorption. In this study we aimed to improve bone regeneration of atrophic non-unions via TNF-α modulation in a previously established murine femoral segmental defect model. Animals that developed atrophic non-unions of the femur after 5 and 10 weeks were treated systemically for 10 and 5 weeks with Etanercept, a soluble TNF-α antibody. μCT scans and histology revealed bony bridging of the fracture gap in the treatment group, while bone formation in control animals without treatment was not evident. Moreover, osteoclasts were markedly decreased via modulation of the RANKL/OPG axis due to Etanercept treatment. Additionally, immunomodulatory effects via Etanercept could be observed as further inflammatory agents, such as TGF-β, IL6, MMP9 and 13 were decreased in both treatment groups. This study is the first showing beneficial effects of Etanercept treatment on bone regeneration of atrophic non-union formation. Moreover, the results of this study provide a new and promising therapeutic option which might reduce the failure rate of revision surgeries of atrophic non-unions.
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http://dx.doi.org/10.1016/j.bone.2020.115569DOI Listing
December 2020

Short-term outcomes of lateral extraction socket augmentation using autogenous tooth roots: A prospective observational study.

Clin Oral Implants Res 2020 Sep 24;31(9):881-888. Epub 2020 Jul 24.

Department of Oral Surgery and Implantology, Goethe University, Carolinum, Frankfurt, Germany.

Objectives: To assess the short-term clinical outcomes of lateral augmentation of deficient extraction sockets and two-stage implant placement using autogenous tooth roots (TR).

Material And Methods: A total of n = 13 patients (13 implants) were available for the analysis. At the time of tooth extraction, each subject had received lateral augmentation using the respective non-retainable but non-infected tooth root where the thickness of the buccal bone was <0.5 mm or where a buccal dehiscence-type defect was present. Titanium implants were placed after a submerged healing period of 6 months and loaded after 20 ± 2 weeks (V8). Clinical parameters (e.g., bleeding on probing-BOP, probing pocket depth-PD, mucosal recession-MR, clinical attachment level-CAL) were recorded at V8 and after 26 ± 4 weeks (V9) of implant loading.

Results: At V9, all patients investigated revealed non-significant changes in mean BOP (-19.23 ± 35.32%), PD (0.24 ± 0.49 mm), MR (0.0 ± 0.0 mm) and CAL (0.24 ± 0.49 mm) values, respectively. There was no significant correlation between the initial gain in ridge width and changes in BOP and PD values.

Conclusions: The surgical procedure was associated with stable peri-implant tissues on the short-term.
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http://dx.doi.org/10.1111/clr.13633DOI Listing
September 2020

Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro.

J Cell Mol Med 2020 08 6;24(16):9332-9348. Epub 2020 Jul 6.

Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.

Sarcomas especially of histiocytic origin often possess a poor prognosis and response to conventional therapies. Interestingly, tumours undergoing mesenchymal to epithelial transition (MET) are often associated with a favourable clinical outcome. This process is characterized by an increased expression of epithelial markers leading to a decreased invasion and metastatic rate. Based on the failure of conventional therapies, viral oncolysis might represent a promising alternative with canine distemper virus (CDV) as a possible candidate. This study hypothesizes that a CDV infection of canine histiocytic sarcoma cells (DH82 cells) triggers the MET process leading to a decreased cellular motility. Immunofluorescence and immunoblotting were used to investigate the expression of epithelial and mesenchymal markers followed by scratch assay and an invasion assay as functional confirmation. Furthermore, microarray data were analysed for genes associated with the MET process, invasion and angiogenesis. CDV-infected cells exhibited an increased expression of epithelial markers such as E-cadherin and cytokeratin 8 compared to controls, indicating a MET process. This was accompanied by a reduced cell motility and invasiveness. Summarized, these results suggest that CDV infection of DH82 cells triggers the MET process by an increased expression of epithelial markers resulting in a decreased cell motility in vitro.
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http://dx.doi.org/10.1111/jcmm.15585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417708PMC
August 2020

Recommendations for Dental Care during COVID-19 Pandemic.

J Clin Med 2020 Jun 12;9(6). Epub 2020 Jun 12.

Department of Oral Surgery and Implantology, Carolinum, Goethe University, Theodor-Stern-Kai 7/Haus 29, 60596 Frankfurt am Main, Germany.

Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.
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http://dx.doi.org/10.3390/jcm9061833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357003PMC
June 2020

Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis.

J Mol Med (Berl) 2020 06 18;98(6):897-906. Epub 2020 May 18.

University Hospital BG Bergmannsheil Bochum, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany.

Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and μ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration Wnt3a restores bone healing after infection Canonical Wnt-pathway activation with negative feedback.
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http://dx.doi.org/10.1007/s00109-020-01924-9DOI Listing
June 2020

RFA measurements of survival midpalatal orthodontic mini-implants in comparison to initial healing period.

Prog Orthod 2020 Feb 17;21(1). Epub 2020 Feb 17.

Department of Orthodontics, Heinrich-Heine-University of Düsseldorf, Moorenstr.5, Building 18.21, 40225, Düsseldorf, Germany.

Background: In dental implantology, the development of stability over time is a well-investigated topic. In case of orthodontic mini-implants, quantitative data for long-term stability is not available yet. This study aims to clinically investigate the long-term stability of mini-implants inserted in the midsagittal suture of the anterior palate. Moreover, the influence of the length of implants was elucidated. The stability of 2 × 9 and 2 × 11 mm mini-implants after orthodontic treatment (9 mm, 2.84 years ± 1.25 years; 11 mm, 3.17 years ± 0.96 years) was assessed by resonance frequency analysis (RFA). The obtained long-term pieces of data were compared with each other (9 mm vs 11 mm), as well as with the data from the matched early stability groups, to assess the initial and early secondary stability after the insertion from previous clinical trials.

Results: For both lengths, the long-term stability (2 × 9 mm, 25.12 ± 7.11, n = 21; 2 × 11 mm, 24.39 ± 5.82, n = 18) was significantly lower than primary stability (2 × 9 mm, 36.14 ± 6.08, n = 19; 2 × 11 mm, 33.35 ± 3.53, n = 20). The differences within the groups disappeared over the initial healing period: after 4 weeks for the 2 × 9 mm implants and after 2 weeks for the 2 × 11 mm implants. Also, the 2 × 9 mm and 2 × 11 mm implants showed comparable long-term stability values.

Conclusion: The stability of midpalatal mini-implants does not change in the long term after the initial healing period. Moreover, 2 × 9 mm mini-implants seem to be appropriate for orthodontic anchorage, as the stability of 2 × 11 mm implants is not higher. Therefore, owing to lower invasiveness, 2 × 9 mm implants should be preferred.
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http://dx.doi.org/10.1186/s40510-020-0305-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024683PMC
February 2020

Can implants move in bone? A longitudinal in vivo micro-CT analysis of implants under constant forces in rat vertebrae.

Clin Oral Implants Res 2019 Dec 26;30(12):1179-1189. Epub 2019 Sep 26.

Department of Orthodontics, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.

Objectives: Whereas stationary stability of implants has been postulated for decades, recent studies suggested a phenomenon termed implant migration. This describes a change in position of implants as a reaction to applied forces. The present study aims at employing image registration of in vivo micro-CT scans from different time points and to assess (a) if migration of continuously loaded implants is possible and (b) migration correlates with the force magnitude.

Material And Methods: Two customized machined implants were placed in the dorsal portion of caudal vertebrae in n = 61 rats and exposed to standardized forces (0.5 N, 1.0 N, and 1.5 N) applied through a flat nickel-titanium contraction spring, or no forces (control). Micro-CT scans were performed at 0, 1, 2, 4, 6, and 8 weeks after surgery. The baseline image was registered with the forthcoming scans. Implant migration was measured as the Euclidean distance between implant tips. Bone remodeling was assessed between the baseline and the forthcoming scans.

Results: The findings confirmed a positional change of the implants at 2 and 8 weeks of healing, and a linear association between applied force and velocity of movement (anterior implant: χ  = 12.12, df = 3, and p = .007 and posterior implant: χ  = 20.35, df = 3, and p < .001). Bone apposition was observed around the implants and accompanied by formation of load-bearing trabeculae and a general cortical thickening close and also distant to the implants.

Conclusion: The present analysis confirmed that implants can migrate in bone. The applied forces seemed to stimulate bone thickening, which could explain why implants migrate without affecting stability.
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http://dx.doi.org/10.1111/clr.13531DOI Listing
December 2019

Is there an ideal insertion angle and position for orthodontic mini-implants in the anterior palate? A CBCT study in humans.

Am J Orthod Dentofacial Orthop 2019 Sep;156(3):345-354

Department for Orthodontics, University Hospital Düsseldorf, Düsseldorf, Germany.

Introduction: Orthodontic mini-implants are frequently used to provide additional anchorage for orthodontic appliances. The anterior palate is frequently used owing to sufficient bone quality and low risk of iatrogenic trauma to adjacent anatomical structures. Even though the success rates in this site are high, failure of an implant will result in anchorage loss. Therefore, implants should be placed in areas with sufficient bone quality. The aim of the present study was to identify an optimal insertion angle and position for orthodontic mini-implants in the anterior palate.

Methods: Maxillary cone-beam computed tomographic (CBCT) scans from 30 patients (8 male, 22 female, age 18.6 ± 12.0 years) were analyzed. To assess the maximum possible length of an implant, a 25-reference-point grid was defined: 5 sagittal slices were extracted along the median plane and bilaterally at 3 mm and 6 mm distances, respectively. Within each slice, 5 dental reference points were projected to the palatal curvature at the contact point between the cuspid (C) and first bicuspid (PM1), midpoint of PM1, between PM1 and PM2, midpoint of PM2, and between PM2 and the first molar (M1). Measurements were conducted at -30°, -20°, -10°, 0°, 10°, 20°, and 30° to a vector placed perpendicular to the local palatal curvature. Statistical analysis was conducted with the use of R using a random-effects mixed linear model and a Tukey post hoc test with Holm correction.

Results: High interindividual variability was detected. Maximum effective bone heights were detected within a T-shaped area at the midpoint of PM1 and contact point PM1-PM2 (P < 0.01). Within the anterior region a posterior tipping was advantageous, whereas in the posterior regions an anterior tipping was beneficial (P < 0.01). In the middle of the median plane, tipping did not reveal a significant influence. No gender- or age-related differences were observed.

Conclusions: Within the limitations of this study, optimal insertion positions were found within a T-shaped area at the height of PM1-PM2 in the anterior palate. In general, a posterior tipping was beneficial at anterior positions, and an anterior tipping appeared beneficial at posterior positions. High interindividual variation was found and should be carefully considered by the clinician.
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http://dx.doi.org/10.1016/j.ajodo.2018.09.019DOI Listing
September 2019

Osteocyte numbers decrease only in postcranial but not in cranial bones in humans of advanced age.

Ann Anat 2019 Nov 19;226:57-63. Epub 2019 Jul 19.

Department of Biosciences, University Salzburg, Hellbrunnerstr 34, 5020 Salzburg, Austria.

Background: Bone ageing is governed by the linked activities of short-lived osteoblasts and osteoclasts in conjunction with long-lived osteocytes present in osseous structure. Besides their maintenance function, osteogenic cells also gain specific positional information, which may potentially trigger ageing-associated cellular deviations in terminally differentiated osteocytes differently in cranial versus postcranial tissues.

Methods: We therefore investigated bone taken from deceased aged humans explanted at five distinct anatomical positions throughout the body and assessed physical and biological determinants applying radiologic and histologic measures.

Results: We were able to show that significantly more osteocytes reside in aged cortical bone at cranial positions than within axial or limb skeleton. These cellular states and conditions were not found in the corresponding trabecular bone, where osteocyte numbers remain also high at postcranial positions. Parallel comparative analyses of bone microstructure as analyzed by means of computer tomography showed no significant differences.

Conclusions: Considering differences and commonalities regarding the bone samples, such as loading, mechanisms of ossification or the surrounding stromal cell compartment, our findings indicate that positional information laid down during ontogenetic processes is instructive during the entire life thus potentially also moulding spatial-specific mechanistic distinctions of bone ageing.
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http://dx.doi.org/10.1016/j.aanat.2019.06.006DOI Listing
November 2019

Short-term outcomes of staged lateral alveolar ridge augmentation using autogenous tooth roots. A prospective controlled clinical study.

J Clin Periodontol 2019 09;46(9):969-976

Department of Oral Surgery, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.

Objectives: To assess the short-term clinical outcomes of lateral alveolar ridge augmentation using autogenous tooth roots (TR) and autogenous bone blocks (AB).

Material And Methods: A total of n = 23 patients (23 implants) were available for the analysis. Each subject was allocated to lateral ridge augmentation using either (a) healthy autogenous tooth roots (e.g., retained wisdom or impacted teeth; n = 13) or (b) cortical autogenous bone blocks harvested from the retromolar area (n = 10). Clinical parameters (e.g., bleeding on probing-BOP, probing pocket depth-PD, mucosal recession-MR, clinical attachment level-CAL) were recorded at (V8) and after 26 ± 4 weeks (V9) of implant loading.

Results: TR and AB groups were associated with comparable (p > 0.05) changes in mean BOP (-23.0 ± 34.3%; -11.75 ± 24.9%), PD (-0.03 ± 0.14 mm; -0.1 ± 0.29 mm), MR (0.0 ± 0.0 mm; 0.0 ± 0.0 mm) and CAL (-0.03 ± 0.14 mm; -0.1 ± 0.29 mm) values. The regression analysis failed to reveal any significant correlations between changes in BOP and PD values and the initial as well as the ridge width measured at 26 weeks.

Conclusions: TR and AB were associated with comparable clinical short-term outcomes.
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http://dx.doi.org/10.1111/jcpe.13161DOI Listing
September 2019

Adipose-Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post-Traumatic Osteomyelitis and Modulate B-Cell Response.

Stem Cells Transl Med 2019 10 10;8(10):1084-1091. Epub 2019 Jun 10.

Department of Plastic Surgery, University Hospital BG Bergmannsheil Bochum, Bochum, Germany.

Bone infections are a frequent cause for large bony defects with a reduced healing capacity. In previous findings, we could already show diminished healing capacity after bone infections, despite the absence of the causing agent, Staphylococcus aureus. Moreover, these bony defects showed reduced osteoblastogenesis and increased osteoclastogenesis, meaning elevated bone resorption ongoing with an elevated B-cell activity. To overcome the negative effects of this postinfectious inflammatory state, we tried to use the regenerative capacity of mesenchymal stem cells derived from adipose tissue (adipose-derived stem cells [ASCs]) to improve bone regeneration and moreover were curious about immunomodulation of applicated stem cells in this setting. Therefore, we used our established murine animal model and applicated ASCs locally after sufficient debridement of infected bones. Bone regeneration and resorption as well as immunological markers were investigated via histology, immunohistochemistry, Western blot, and fluorescence-activated cell scanning (FACS) analysis and μ-computed tomography (CT) analysis. Interestingly, ASCs were able to restore bone healing via elevation of osteoblastogenesis and downregulation of osteoclasts. Surprisingly, stem cells showed an impact on the innate immune system, downregulating B-cell population. In summary, these data provide a fascinating new and innovative approach, supporting bone healing after bacterial infections and moreover gain insights into the complex ceremony of stem cell interaction in terms of bone infection and regeneration. Stem Cells Translational Medicine 2019;8:1084-1091.
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http://dx.doi.org/10.1002/sctm.18-0266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766598PMC
October 2019

Autogenous tooth roots for lateral extraction socket augmentation and staged implant placement. A prospective observational study.

Clin Oral Implants Res 2019 May 22;30(5):439-446. Epub 2019 Apr 22.

Department of Oral Surgery, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.

Objectives: To assess the feasibility of using autogenous tooth roots (TR) for a lateral augmentation of deficient extraction sockets and two-stage implant placement.

Material And Methods: A total of 15 patients were recruited to perform a simultaneous, lateral augmentation of deficient (i.e., thickness of the buccal bone < 0.5 mm or buccal dehiscence-type defects) fresh extraction sockets using the respective non-retainable but non-infected teeth (n = 15). After 26 weeks of submerged healing, the primary endpoint was defined as the crestal ridge width (mm) (CW26) being sufficient to place an adequately dimensioned titanium implant at the respective sites.

Results: The surgical procedure could be accomplished in n = 14 patients. Soft tissue healing was uneventful in all patients. CW26 at visit 6 allowed for a successful implant placement in all patients (e.g., 14/14). Mean CW26 values amounted to 10.85 ± 2.71 mm (median: 8.5). The change (4.89 ± 2.29 mm) in CW compared to baseline was statistically significant (p < 0.001).

Conclusions: The usage of TR may represent a feasible approach for lateral augmentation of deficient extraction sockets and two-stage implant placement.
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http://dx.doi.org/10.1111/clr.13429DOI Listing
May 2019

Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

Arch Toxicol 2019 04 12;93(4):1095-1139. Epub 2019 Feb 12.

Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.
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http://dx.doi.org/10.1007/s00204-019-02400-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261740PMC
April 2019
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