Gender- and age-related differences in the width of attached gingiva and clinical crown length in anterior teeth

Background: The anatomical features of the gingiva and the clinical crowns and their interrelation, especially in aesthetically and functionally demanding areas, are important in complex dental or implant-retained prosthetic rehabilitations. This observational cross-sectional study was designed to evaluate gender- and age-related differences in the width of attached gingiva (WAG), the clinical crown length (CCL), and their interrelation in the anterior teeth to determine the relationship between the pink and white aesthetics. Methods: Eighty (54 females, 26 males) fully dentate Caucasian participants between the ages of 20 and 25 years and 36 probands (23 females, 13 males) between the ages of 45 and 55 years were included in the present study. The CCL of the maxillary and mandibular canines, as well as the central incisors of the maxilla and mandible, were determined with a dental sliding caliper measuring from the middle margin of the gingiva at its deepest point to the incisal edge. The clinical investigation of the WAG was performed by inserting a periodontal probe into the gingival sulcus in the middle of the buccal surface to firstly measure the probing pocket depth. The distance between the gingival margin and mucogingival junction (MGJ) was then measured with a Beerendonk sliding caliper in the middle of the labial curvature, and the clinical WAG was determined by subtraction of the measured probing depth. For the statistical analysis, the Mann-Whitney U test, the Wilcoxon-Test, the Spearman's rank correlation, and a two-factorial non-parametric analysis were used. Results: There was no correlation between the CCL and the WAG in a healthy periodontium. Gender influenced the CCL, with men having significantly longer teeth than women in both maxilla (P <= 0.01) and mandible (P <= 0.05). Age did not influence the CCL significantly neither in the upper (P=0.06) nor in the lower jaw (P=0.33). Gender did not show to have a significant influence on the WAG of maxilla (P=0.69) and mandible (P=0.26). But differences in the WAG between young and old participants were observed in both upper (P <= 0.01) and lower jaw (P <= 0.05). Conclusion: The present observational study demonstrated that the mean values of cohorts with mixed age groups and genders should not be considered when attempting to determine the ideal relationships between the pink and white aesthetics since the statistical analyses showed significant differences between different age groups and genders

Influence of implant‐specific radiation doses on peri‐implant hard and soft tissue: An observational pilot study

Objectives: The aim of this study was to investigate the influence of real implant-bed-specific radiation doses on peri-implant tissue health in head and neck cancer (HNC) patients after radiotherapy. Material and methods: Specific radiation doses in the area of 81 implants, in 15 irradiated HNC patients, were analyzed by matching data from the radiotherapy planning system with those of three-dimensional follow-up scans after implantation. Peri-implant bone resorption was measured radiographically after 1 and 3 years, and peri-implant tissue health was evaluated clinically. Individual parameters, such as age, gender, and localization, regarding the implant-specific radiation dose distribution were analyzed statistically. Results: The mean implant-bed-specific radiation dose was high, with 45.95 Gy to the mandible and 29.02 Gy to the maxilla, but significantly lower than the mean total dose to the tumor bed. Peri-implant bone resorption correlated with local inflammation and plaque. After 1 year, women temporarily showed significantly more bone loss than men and implant-specific radiation dose had a significant impact on peri-implant bone loss after 3 years. Conclusions: The presented method is a feasible option to define precise implant-bed-specific radiation doses for research or treatment planning purposes. Implant-based dental restoration after radiotherapy is a relatively safe procedure, but a negative radiation dose-dependent long-term effect on peri-implant bone resorption calls for interdisciplinary cooperation between surgeons and radio-oncologists to define high-risk areas

Philosophie der Lebenswissenschaften

This paper summarizes (in German) recent tendencies in the philosophy of the life sciences

Philosophie der Lebenswissenschaften: Entwicklungen und Tendenzen

Bauer S, Huber L, Kaiser MI, et al. Philosophie der Lebenswissenschaften: Entwicklungen und Tendenzen. Information Philosophie. 2013;4:14-27.Eine gemeinsame Publikation des Netzwerks Philosophie der Lebenswissenschaften über Entwicklungen und Trends in der philosophischen Auseinandersetzung mit den Lebenswissenschaften. Gegenstand sind v.a. neue Debatten zu Begriffen aus der allgemeinen Wissenschaftsphilosophie, Hinwendung zur Praxis, Hinwendung zu neuen Feldern. Dabei kommen folgende Themen v.a. zur Sprache: natural kinds, Reduktion, synthetische Biologie, Robustheit von Daten, Anthropologie

Impact of radiotherapy and sequencing of systemic therapy on survival outcomes in melanoma patients with previously untreated brain metastasis: a multicenter DeCOG study on 450 patients from the prospective skin cancer registry ADOREG

BACKGROUND: Despite of various therapeutic strategies, treatment of patients with melanoma brain metastasis (MBM) still is a major challenge. This study aimed at investigating the impact of type and sequence of immune checkpoint blockade (ICB) and targeted therapy (TT), radiotherapy, and surgery on the survival outcome of patients with MBM. METHOD: We assessed data of 450 patients collected within the prospective multicenter real-world skin cancer registry ADOREG who were diagnosed with MBM before start of the first non-adjuvant systemic therapy. Study endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Of 450 MBM patients, 175 (38.9%) received CTLA-4+PD-1 ICB, 161 (35.8%) PD-1 ICB, and 114 (25.3%) BRAF+MEK TT as first-line treatment. Additional to systemic therapy, 67.3% of the patients received radiotherapy (stereotactic radiosurgery (SRS); conventional radiotherapy (CRT)) and 24.4% had surgery of MBM. 199 patients (42.2%) received a second-line systemic therapy. Multivariate Cox regression analysis revealed the application of radiotherapy (HR for SRS: 0.213, 95% CI 0.094 to 0.485, p1 cm: 1.977, 95% CI 1.117 to 3.500, p=0.019), age (HR for age >65 years: 1.802, 95% CI 1.016 to 3.197, p=0.044), and ECOG performance status (HR for ECOG ≥2: HR: 2.615, 95% CI 1.024 to 6.676, p=0.044) as independent prognostic factors of OS on first-line therapy. The type of first-line therapy (ICB vs TT) was not independently prognostic. As second-line therapy BRAF+MEK showed the best survival outcome compared with ICB and other therapies (HR for CTLA-4+PD-1 compared with BRAF+MEK: 13.964, 95% CI 3.6 to 54.4, p<0.001; for PD-1 vs BRAF+MEK: 4.587 95% CI 1.3 to 16.8, p=0.022 for OS). Regarding therapy sequencing, patients treated with ICB as first-line therapy and BRAF+MEK as second-line therapy showed an improved OS (HR for CTLA-4+PD-1 followed by BRAF+MEK: 0.370, 95% CI 0.157 to 0.934, p=0.035; HR for PD-1 followed by BRAF+MEK: 0.290, 95% CI 0.092 to 0.918, p=0.035) compared with patients starting with BRAF+MEK in first-line therapy. There was no significant survival difference when comparing first-line therapy with CTLA-4+PD-1 ICB with PD-1 ICB. CONCLUSIONS: In patients with MBM, the addition of radiotherapy resulted in a favorable OS on systemic therapy. In BRAF-mutated MBM patients, ICB as first-line therapy and BRAF+MEK as second-line therapy were associated with a significantly prolonged OS

Changes in magnetic resonance mammography due to hormone replacement therapy

BACKGROUND: The aim of the present article is to investigate effects of hormone replacement therapy (HRT) on contrast medium enhancement patterns in postmenopausal patients during magnetic resonance mammography (MRM). MATERIALS AND METHODS: Two hundred and fifteen patients receiving hormonal medication were divided into four groups: 150 patients with 1 MRM during HRT (group A), 13 patients with 2 MRMs under HRT (group B), 30 patients with 1 MRM during HRT and 1 MRM after HRT withdrawal (group C), and 22 women with 1 MRM after HRT withdrawal (group D). Dynamic MRM was performed at 1.5 Tesla. Signal intensity changes were characterized by five time curves: minimal enhancement (type I), weak continuous enhancement (type II), strong continuous enhancement (type III), and a steep initial slope followed by a plateau phenomenon (type IV) or a washout effect (type V). RESULTS: Of all 193 patients under HRT (group A + group B + group C), 60 patients (31.1%) showed curve type I, 88 patients (45.6%) showed type II and 45 patients (23.3%) showed type III. There were significant differences to 52 patients after HRT withdrawal (group C + group D) (P < 0.0001), with 42 patients (80.8%) for curve type I, 8 patients (15.4%) for type II, and 2 patients (3.8%) for type III. In both MRM sessions in group B, 69% of the patients showed identical curve types without significant differences (P = 0.375). In group C, 28 of 30 patients (93%) dropped to lower curve types with significant differences in curve types during and after HRT (P < 0.0001). CONCLUSION: The majority of patients receiving postmenopausal HRT showed bilateral symmetrical, continuous enhancement without evidence of a plateau phenomenon or a washout effect due to HRT in MRM. Hormonal effects could be proven and were reproducible and reversible

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.Methods Patients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).Results Of 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwt patients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmut patients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmut patients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmut patients. In BRAFwt patients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwt patients. For BRAFmut patients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.Conclusions In BRAFmut patients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwt patients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1

The Kaiser Wilhelm Society under National Socialism

During the first part of the twentieth century, German science led the world. The most important scientific institution in Germany was the Kaiser Wilhelm Society, including institutes devoted to different fields of scientific research. These researchers were not burdened by teaching obligations and enjoyed excellent financial and material support. When the National Socialists came to power in Germany, all of German society, including science, was affected. The picture that previously dominated our understanding of science under National Socialism from the end of the Second World War to the recent past - a picture of leading Nazis ignorant and unappreciative of modern science and of scientists struggling to resist the Nazis - needs to be revised. This book surveys the history of Kaiser Wilhelm Institutes under Hitler, illustrating definitively the cooperation, if not collaboration, between scientists and National Socialists in order to further the goals of autarky, racial hygiene, war, and genocide

Brain Research and the Murder of the Sick: The Kaiser Wilhelm Institute for Brain Research, 1937 – 1945

Schmuhl H-W. Brain Research and the Murder of the Sick: The Kaiser Wilhelm Institute for Brain Research, 1937 – 1945. In: Heim S, Sachse C, Walker M, eds. The Kaiser Wilhelm Society under National Socialism. Cambridge; 2009: 99-119

Membrane protein synthesis in cell-free systems: From bio-mimetic systems to bio-membranes

AbstractWhen taking up the gauntlet of studying membrane protein functionality, scientists are provided with a plethora of advantages, which can be exploited for the synthesis of these difficult-to-express proteins by utilizing cell-free protein synthesis systems. Due to their hydrophobicity, membrane proteins have exceptional demands regarding their environment to ensure correct functionality. Thus, the challenge is to find the appropriate hydrophobic support that facilitates proper membrane protein folding. So far, various modes of membrane protein synthesis have been presented. Here, we summarize current state-of-the-art methodologies of membrane protein synthesis in biomimetic-supported systems. The correct folding and functionality of membrane proteins depend in many cases on their integration into a lipid bilayer and subsequent posttranslational modification. We highlight cell-free systems utilizing the advantages of biological membranes