Periodontal health literacy in Germany-Results of a telephone survey.

OBJECTIVE: Assess the periodontal health literacy of German adolescents, adults and senior residents. BACKGROUND: The prevalence of periodontitis is high. One explanation for this may be that people lack periodontal health literacy (PHL). METHODS: This was a cross-sectional descriptive study. Former participants of the 5th German Oral Health Study (n = 333 16-year-olds, n = 307 39-48-year-olds, n = 332 69-78-year-olds) participated in a computer-assisted telephone interview. Open-ended questions (OEQs) were used to assess the participants' current knowledge. Corresponding single- and multiple-choice questions (SCQs and MCQs) supplemented the OEQs to allow detailed analyses of the nature of the knowledge gaps. RESULTS: Less than 10% of the participants in the three age groups could explain the term 'periodontitis' or select the correct answer in an SCQ. Responding to the OEQs, 89% of 16-year olds, 64% of 39-48-year-olds, and 59% of 69-78-year-olds, could not name any consequence of periodontitis, and 83%, 51%, and 60%, respectively, could not name any risk factors. The OEQs regarding proper oral hygiene behaviour revealed that participants lacked awareness regarding important aspects of oral hygiene (e.g., systematics) or areas to which they should pay attention to (e.g., interdental spaces and gingival margins). CONCLUSIONS: The survey revealed PHL deficits in German adolescents, adults, and seniors and a need for community-based measures to improve PHL in all age groups. Dental teams should be aware that their patients might lack the PHL necessary for understanding and adherence to professional dental advice, and that they might even lack PHL regarding the proper use of oral hygiene devices.

Prevalence of malocclusions in 8- and 9-year-old children in Germany-Results of the Sixth German Oral Health Study (DMS 6).

PURPOSE: Current population-wide data on the prevalence of malocclusions in 8­ and 9­year-old children in Germany are not available. Therefore, the primary objective of this study was to collect data on the prevalence of malocclusions in 8­ and 9­year-old children in Germany. The secondary objective of this study was to use this information to derive the need for orthodontic care provision. METHODS: This is an oral-epidemiological investigation and social science survey at the national level with a focus on tooth and jaw misalignment. The investigation took place between January and March 2021 at 16 study centers across Germany. All relevant data were available for the 705 study participants and were included in the statistical analysis. RESULTS: Overbite was the most common finding with 88.9%. Also widespread were crowding, with at least 60.9%, and lack of space, with a share of 30.9%. All other indication groups had a share below 10%. Rare (< 1%) were buccal and lingual occlusions and craniofacial abnormalities. The most severe forms of disease (Orthodontic Indication Group [Kieferorthopädische Indikationsgruppen, KIG] grade 5) were overbite (3.2%), open bite malocclusion (1.0%), undershot (0.6%), and craniofacial abnormalities (0.4%). The proportion of study participants who required orthodontic treatment, in accordance with statutory health insurance provider guidelines, was 40.4%. The proportion of study participants in principle requiring orthodontic treatment for medical reasons was 97.5%. Systemic differences in the need for orthodontic care provision relating to gender, region, or social status were not identified. CONCLUSION: In general, the need for care provision identified in the orthodontic indication groups corresponds to that shown in previous studies. This suggests that the need for orthodontic treatment in Germany has remained stable over the years.

Methodology of the Sixth German Oral Health Study (DMS 6) to survey tooth and jaw misalignment.

PURPOSE: The aim of this study was (1) to complete and update the oral-epidemiological data situation in Germany (descriptive epidemiology) and (2) to determine the need for orthodontic treatment provision based on the epidemiological data situation (health care epidemiology in the form of demand research). METHODS: For this purpose, a longitudinal oral-epidemiological study and social science survey with a primary focus on tooth and jaw misalignment was conducted at a nationally representative level on 705 8­ and 9­year-old children across Germany. RESULTS: The methodological principles of the oral-epidemiological study are described, with a focus on the calibration and reliability assessment results from the study dentists, sample weighting, a survey of nonrespondents to estimate the extent of the external validity of the study results, a description of the study participants, and realized cases, as well as information pertaining to the response rate and utilization. CONCLUSION: Based on the conducted analyses, it can be assumed that the examined 8­ and 9­year-old study participants are representative of the statistical population in Germany.

Does orthodontic treatment need have an impact on oral health-related quality of life?

OBJECTIVES: The aims of this study were to determine the frequency of oral health-related quality of life (OHRQoL) impairment in a national representative sample of 8 to 9 year olds in Germany and to evaluate the impact of orthodontic treatment need. METHODS: Data were collected in the Sixth German Oral Health Study (Sechste Deutsche Mundgesundheitsstudie, DMS 6) and subjects were sampled using a multistage sampling technique. OHRQoL was measured with a modified version of the 5­item Oral Health Impact Profile (OHIP-5) which was administered in a computer-assisted personal interview. Children were also examined for malocclusion and orthodontic treatment need. RESULTS: In all, 1892 children aged 8-9 years were invited to take part. Finally, data of 705 children (48.6% female) could be included in the analysis. The OHIP­5 mean was 1.3 (±2.0). There was no relevant influence from age and gender on the OHIP­5 summary scores (r < 0.10), but the summary scores differed when analyzed separately regarding orthodontic treatment need or no orthodontic treatment need (1.5 ± 2.0 vs. 1.2 ± 1.9, p = 0.020). Nevertheless, the level appears to be low. CONCLUSIONS: Malocclusions with orthodontic treatment need have an influence on OHRQoL.

Comparison of orthodontic treatment need and malocclusion prevalence according to KIG, ICON, and mIOTN in German 8- to 9-year-old children of the Sixth German Oral Health Study (DMS 6).

PURPOSE: The aim of the present study was to compare the malocclusion indices KIG (Kieferorthopädische Indikationsgruppen, Orthodontic Indication Groups), ICON (Index of Complexity, Outcome and Need), and mIOTN (modified Index of Orthodontic Treatment Need) regarding differences in malocclusion prevalence and their assessment of orthodontic treatment need in German 8­ to 9­year-old children of the Sixth German Oral Health Study (Deutsche Mundgesundheitsstudie, DMS 6). METHODS: The necessary data for the calculation of the KIG, mIOTN, and ICON were collected by a dentist as part of a clinical orthodontic examination during the field phase of the DMS 6 and by a subsequent digital orthodontic model-analytical evaluation of intraoral scans of the dental arches and the occlusal situation in habitual occlusion. RESULTS: Prevalence, severity, and treatment need of tooth and jaw misalignments differed in part considerably depending on the index used for assessment. On the other hand, there were several outcomes which yielded quite similar results for the different indices used, such as orthodontic treatment need, which ranged from 40.4% (KIG) over 41.6% (ICON) to 44.2% (mIOTN). Interestingly, orthodontic treatment need for the individual subject could differ considerably, when assessed using different indices. CONCLUSIONS: In general, the results show that the mIOTN is much more conservative in assessing malocclusion prevalences often being smaller than those derived by KIG or ICON. In contrast, KIG and ICON often yield similar prevalences with certain distinct differences due to discrepancies in the respective definitions and also clearly differentiate between treatment possibility and arbitrarily determined treatment need.

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme.

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan-Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6-16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.

Magnetic nanoparticle hyperthermia for prostate cancer.

Magnetic nanoparticles are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. A novel method of interstitial heating of tumours following direct injection of magnetic nanoparticles has been evaluated in humans in recent clinical trials. In prostate cancer this approach has been investigated in two separate phase I studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of an alternating magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography was validated. Limiting factors of the new approach at present are patient discomfort at high magnetic field strengths and irregular intratumoural heat distribution. Until these limitations are overcome and thermoablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localised prostate cancer.

Hyperthermia classic commentary: 'Inductive heating of ferrimagnetic particles and magnetic fluids: Physical evaluation of their potential for hyperthermia' by Andreas Jordan et al., International Journal of Hyperthermia, 1993;9:51-68.

In order to increase the specific power absorption (SAR) in deep seated tumors, the idea was born to use AC magnetic fields in combination with magnetic particles instead of conventional E-field dominant systems. It was found, that nanoscaled particles were superior to micron-sized, multi-domain particles in terms of SAR due to different mechanisms how the field energy is converted into heat. Crucial parameters were identified for the human application of the method, such as the AC magnetic field amplitude and frequency, the nanoparticle composition and size distribution. Based on these physical and chemical relationships, a new thermotherapy method has been developed to heat up deep regional tumors using aqueous dispersions of iron oxide nanoparticles (magnetic fluids). Several clinical studies were initiated using this new heating technology. The results of the most advanced efficacy study for recurrent glioblastoma multiforme patients in combination with conventional radiation therapy are expected at the end of this year, 16 years after publication of this fundamental paper.

Clinical applications of magnetic nanoparticles for hyperthermia.

Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio- or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.

Side Effects and Interactions of the Xanthine Oxidase Inhibitor Febuxostat.

The paper addresses the safety of febuxostat and summarizes reports on side effects and interactions of febuxostat published by the cut-off date (last day of literature search) of 20 March 2018. Publications on side effects and the interactions of febuxostat were considered. Information concerning the occurrence of side effects and interactions in association with the treatment with febuxostat was collected and summarized in the review. The incidence of severe side effects was much less frequent than mild side effects (1.2⁻3.8% to 20.1⁻38.7%). The rate and range of febuxostat side effects are low at doses of up to 120 mg and only increase with a daily dose of over 120 mg. The publications reveal no age-dependent increase in side effects for febuxostat. In patients with impaired renal function, no increase in adverse events is described with a dose of up to 120 mg of febuxostat per day. Patients with impaired liver function had no elevated risk for severe side effects. A known allopurinol intolerance increases the risk of skin reactions during treatment with febuxostat by a factor of 3.6. No correlation between treatment with febuxostat and agranulocytosis has been confirmed. Possible interactions with very few medications (principally azathioprine) are known for febuxostat. Febuxostat is well tolerated and a modern and safe alternative to allopurinol therapy.

Magnetic nanoparticles for intracranial thermotherapy.

Thermotherapy using magnetic nanoparticles, also termed nanotherapy, is a new therapeutic concept in which tumor cells are damaged via local heat application. The principle of this method is direct injection of a magnetic fluid into a tumor and its subsequent heating in an alternating magnetic field. The heat created this way (thermotherapy) causes either direct damage to the tumor cells (depending on temperature and reaction time) or make cells more susceptible to accompanying radio- or chemotherapy. The results of a feasibility trial (phase I) on the treatment of brain tumors (glioblastoma multiforme) are presented.

[Thermal therapy of prostate cancer using magnetic nanoparticles]. / Termoterapia en cáncer de próstata mediante el uso de nanopartículas magnéticas.

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.

Local arterial infusion of superparamagnetic iron oxide particles in hepatocellular carcinoma: A feasibility and 3.0 T MRI study.

OBJECTIVES: We sought to prove feasibility of selective arterial infusion of superparamagnetic iron oxide (SPIO) particles in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We studied 13 patients with HCC who underwent modified transarterial chemoembolization (TACE). Six patients received concurrent infusion of Ferucarbotran (Resovist, Schering, Berlin, Germany) in tumor-feeding arteries, and another 6 received MFL AS (MagForce, Nanotechnologies, Berlin, Germany). The iron content of both dispersions was 3.92 mg. One patient served as a control. All patients underwent magnetic resonance imaging (MRI) as baseline and immediate follow-up investigation. RESULTS: Selective arterial infusion of both SPIO particles resulted in significant intratumoral signal intensity decrease on T1-weighted sequences (P < 0.0001), which was greater after MagForce infusion compared with Resovist (P = 0.002). Only minimal amounts of dispersed particles were found in adjacent normal liver parenchyma. No change in intratumoral signal intensity was noted when ferromagnetic particles were omitted. CONCLUSIONS: Modified TACE with selective arterial infusion of SPIO particles can be used for precise tumor targeting in patients with HCC, for which MagForce appeared superior to Resovist.

SV40 large T-antigen disturbs the formation of nuclear DNA-repair foci containing MRE11.

The accumulation of DNA repair proteins at the sites of DNA damage can be visualized in mutagenized cells at the single cell level as discrete nuclear foci by immunofluorescent staining. Formation of nuclear foci in irradiated human fibroblasts, as detected by antibodies directed against the DNA repair protein MRE11, is significantly disturbed by the presence of the viral oncogene, SV40 large T-antigen. The attenuation of foci formation was found in both T-antigen immortalized cells and in cells transiently expressing T-antigen, indicating that it is not attributable to secondary mutations but to T-antigen expression itself. ATM-mediated nibrin phosphorylation was not altered, thus the disturbance of MRE11 foci formation by T-antigen is independent of this event. The decrease in MRE11 foci was particularly pronounced in T-antigen immortalized cells from the Fanconi anaemia complementation group FA-D2. FA-D2 cells produce essentially no MRE11 DNA repair foci after ionizing irradiation and have a significantly increased cellular radiosensitivity at low radiation doses. The gene mutated in FA-D2 cells, FANCD2, codes for a protein which also locates to nuclear foci and may, therefore, be involved in MRE11 foci formation, at least in T-antigen immortalized cells. This finding possibly links Fanconi anaemia proteins to the frequently reported increased sensitivity of Fanconi anaemia cells to transformation by SV40. From a practical stand point these findings are particularly relevant to the many studies on DNA repair which exploit the advantages of SV40 immortalized cell lines. The interference of T-antigen with DNA repair processes, as demonstrated here, should be borne in mind when interpreting such studies.

Iodinated nitroimidazoles as radiosensitizers.

Four different nitroimidazole derivatives, with up to two iodine atoms on the imidazole ring, were investigated for their radiosensitizing potency under hypoxic conditions, in order to test whether the introduction of iodine atoms increases the radiosensitizing potency of nitroimidazoles. Misonidazole and metronidazole were used as controls. Human colonic adenocarcinoma cells were incubated with the drugs at different concentrations and for different time-periods. Photon energies of 50 kV, 60 kV and 20 MV and total radiation doses of up to 20 Gy were used. The introduction of additional iodine atoms into the nitroimidazole derivatives resulted in a strong increase in cytotoxicity of the compounds. In parallel, there were indications that the radiosensitizing potency was also increased.

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells.

Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer) as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs) and silica-coated iron oxide nanoparticles (SCIONs) between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

Description and characterization of the novel hyperthermia- and thermoablation-system MFH 300F for clinical magnetic fluid hyperthermia.

Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep tissues by overcoming limitations of conventional heat treatments. After infiltration of the target tissue with nanosized magnetic particles, the power of an alternating magnetic field is transformed into heat. The combination of the 100 kHz magnetic field applicator MFH 300F and the magnetofluid (MF), which both are designed for medical use, is investigated with respect to its dosage recommendations and clinical applicability. We found a magnetic field strength of up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture height up to 300 mm. The specific absorption rate (SAR) can be controlled directly by the magnetic field strength during the treatment. The relationship between magnetic field strength and the iron normalized SAR (SAR(Fe)) is only slightly depending on the concentration of the MF and can be used for planning the target SAR. The achievable energy absorption rates of the MF distributed in the tissue is sufficient for either hyperthermia or thermoablation. The fluid has a visible contrast in therapeutic concentrations on a CT scanner and can be detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and practicability for heat treatment in deep regions of the human body.

Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate cancer.

PURPOSE: To examine the feasibility and potential of magnetic fluid hyperthermia (MFH) as a minimally invasive method for hyperthermia treatment of prostate cancer. MATERIALS AND METHODS: Orthotopic Dunning R3327 prostate tumors were induced in 20 male Copenhagen rats. The animals either received MFH treatment following intratumoral administration of magnetic fluids or were used as either tumor growth controls for determination of iron distribution in selected organs or as histologic controls without MFH treatment. The MFH treatments were carried out at 45 degrees C or 50 degrees C using an AC magnetic field applicator system designed for small animals. RESULTS: Sequential treatments with MFH were possible following a single intratumoral injection of magnetic fluid. Intratumoral temperatures of 50 degrees C and more were obtained and were monitored online using fluoro-optic thermometry. Four days after MFH treatments, 79% of the injected dose of ferrites was still present in the prostate. CONCLUSIONS: The successful intraprostatic nanoparticle infiltration and stable steady-state intratumoral treatment temperatures demonstrate the feasibility of MFH in a prostate cancer model. Efficacy and survival benefit must be confirmed in further experiments.

Modification of aminosilanized superparamagnetic nanoparticles: feasibility of multimodal detection using 3T MRI, small animal PET, and fluorescence imaging.

PURPOSE: The aim of our study was to modify an aminosilane-coated superparamagnetic nanoparticle for cell labeling and subsequent multimodal imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescent imaging in vivo. PROCEDURES: We covalently bound the transfection agent HIV-1 tat, the fluorescent dye fluorescein isothiocyanate, and the positron-emitting radionuclide gallium-68 to the particle and injected them intravenously into Wistar rats, followed by animal PET and MRI at 3.0 T. As a proof of principle hepatogenic HuH7 cells were labeled with the particles and observed for cell toxicity as well as detectability by MRI and biodistribution in vivo. RESULTS: PET imaging and MRI revealed increasing hepatic and splenic accumulation of the particles over 24 h. Adjacent in vitro studies in hepatogenic HuH7 cells showed a rapid intracellular accumulation of the particles with high labeling efficiency and without any signs of toxicity. In vivo dissemination of the labeled cells could be followed by dynamic biodistribution studies. CONCLUSIONS: We conclude that our modified superparamagnetic nanoparticles are stable under in vitro and in vivo conditions and are therefore applicable for efficient cell labeling and subsequent multimodal molecular imaging. Moreover, their multiple free amino groups suggest the possibility for further modifications and might provide interesting opportunities for various research fields.

A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.

BACKGROUND: The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals. METHODOLOGY/PRINCIPAL FINDINGS: We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs. CONCLUSIONS/SIGNIFICANCE: In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress.