Prevalence of KIG-grades 3–5 in an orthodontic practice in North Rhine Westphalia compared with results of the DMS•6 and with KZBV data

Background and aim The prevalence of tooth and jaw malocclusions in 8- to 9-year-olds was surveyed in a nationwide setting as part of the orthodontic module of the Sixth German Study on Oral Health (DMS•6), using the orthodontic indication groups (KIG) as index. Aim of this study was the detection of the prevalence of malocclusions requiring treatment according to the KIG index in statutorily insured patients of an orthodontic practice in North Rhine Westphalia, Germany, and to compare results with corresponding DMS•6 and KZBV data. Patients and methods Between 2017–2021, n=953 statutorily insured patients called for an initial consultation and subsequent determination of the KIG-classifcation and -grades. The malocclusions were classifed and graded in the highest possible KIG-grade according to valid SHI guidelines. Multiple classifcations were not recorded. KIG-grade>3 according to the valid guidelines was detected in n=815 patients. Since the DMS•6 does not contain information on KIG classifcations "U" and "S", their inclusion was waived despite evaluation, leaving data from n=683 patients for analysis and comparison. Results During the study period, n=235 patients (34.4%) had KIG-classifcation "D". More than 10% were classifed as "K" (120 patients, 17.6%), "P" (98 patients, 14.2%), "M" (89 patients, 13.0%), and "E" (81 patients, 11.9%). Of 16 possible classifcations with KIG-grade>3, "D4" was the most common with 26.6% (182 patients). The results confrm the fndings from the multicentric DMS•6 from2021 and corresponding KZBV data from 2020. Conclusions Sagittal deviations described by classifcations "D" and "M" represent with 47.4% almost half of the malocclusions with treatment need. KIG-grade D4 is the most frequent classifcation. There were no regional deviations of the prevalence of KIG-grades 3–5 in the district of Viersen / North Rhine compared with the national average, not even when scrutinizing a fve-year-period

Effects on cardiorespiratory fitness of moderate-intensity training vs. energy-matched training with increasing intensity

Introduction: The present study investigated the role of training intensity in the dose–response relationship between endurance training and cardiorespiratory fitness (CRF). The hypothesis was that beginners would benefit from an increase in training intensity after an initial training phase, even if the energy expenditure was not altered. For this purpose, 26 weeks of continuous moderate training (control group, CON) was compared to training with gradually increasing intensity (intervention group, INC) but constant energy expenditure. Methods: Thirty-one healthy, untrained subjects (13 men, 18 women; 46 ± 8 years; body mass index 25.4 ± 3.3 kg m−2 ; maximum oxygen uptake, VO2max 34 ± 4 ml min−1 kg−1 ) trained for 10 weeks with moderate intensity [3 days/ week for 50 min/session at 55% heart rate reserve (HRreserve)] before allocation to one of two groups. A minimization technique was used to ensure homogeneous groups. While group CON continued with moderate intensity for 16 weeks, the INC group trained at 70% HRreserve for 8 weeks and thereafter participated in a 4 × 4 training program (high-intensity interval training, HIIT) for 8 weeks. Constant energy expenditure was ensured by indirect calorimetry and corresponding adjustment of the training volume. Treadmill tests were performed at baseline and after 10, 18, and 26 weeks. Results: The INC group showed improved VO2max (3.4 ± 2.7 ml kg−1 min−1 ) to a significantly greater degree than the CON group (0.4 ± 2.9 ml kg−1 min−1 ) (P = 0.020). In addition, the INC group exhibited improved Vmax (1.7 ± 0.7 km h−1 ) to a significantly greater degree than the CON group (1.0 ± 0.5 km h−1 ) (P = 0.001). The reduction of resting HR was significantly larger in the INC group (7 ± 4 bpm) than in the CON group (2 ± 6 bpm) (P = 0.001). The mean heart rate in the submaximal exercise test was reduced significantly in the CON group (5 ± 6 bpm; P = 0.007) and in the INC group (8 ± 7 bpm; P = 0.001), without a significant interaction between group and time point

Comparative Analysis of the Visual, Refractive and Aberrometric Outcome with the Use of 2 Intraocular Refractive Segment Multifocal Lenses

To demonstrate the results of ray tracing higher- and lower-order aberrations in pseudophakic eyes with rotationally asymmetrical segment multifocal lenses, total high- and low-order aberrations, measured by root mean square value (RMS), refraction, uncorrected distance and uncorrected near visual acuity (UCDVA and UCNVA), and tear break-up time, were measured at scotopic size in 42 eyes of patients implanted with bifocal refractive Mplus15/Mplus30 IOL with +1.5 dpt near addition (42 eyes of patients implanted with Mplus15)/+3.0 dpt near addition (91 eyes of patients implanted with Mplus30), and 107 eyes of control group. No significant differences were noticed between the examined groups concerning UCDVA, UCNVA, and tear break-up time (p < 0.001). Coma and total high-order aberrations were significantly higher for the Mplus30 lens in comparison to the Mplus15 lens and the control group (Coma, Trefoil p < 0.001, Secondary Astigmatism p = 0.002). The spherical aberrations were significantly higher in the lower-addition lens (p = 0.016) in comparison to the control group and to the higher-addition lens group (p < 0.001). Both intraocular lens models were successful at reaching refractive aim, good distance, and near function with the lower higher-order aberrations for the low-addition lens

Projektbericht: Summa Cum Fraude – Wissenschaftliches Fehlverhalten und der Versuch einer Gegenoffensive. Öffentlicher Teil

Das Projekt befasste sich mit der zentralen Fragestellung, inwieweit die bestehenden Mechanismen zur Selbstkontrolle in der Wissenschaft in der Lage sind, wissenschaftlichem Fehlverhalten effektiv entgegenzuwirken. Es wurden 207 Fälle von wissenschaftlichem Fehlverhalten ausführlich dokumentiert und an die betroffenen Verlage gemeldet. Dabei kamen nur solche Fälle zur Meldung, bei denen die Indikatoren für wissenschaftliches Fehlverhalten eindeutig waren (z.B. war die Manipulation von Daten mit bloßem Auge erkennbar). Leider hat sich schnell herausgestellt, dass selbst in diesen eindeutigen Fällen das tatsächliche Handeln durch die Journale von den in den ethischen Grundsätzen der Verlage formulierten Richtlinien zum Umgang mit wissenschaftlichem Fehlverhalten in der Mehrzahl der Fälle nahezu diametral abweicht. In vielen Fällen kann von einem Handeln nicht einmal die Rede sein, da Journale selbst auf wiederholte Meldungen desselben Falles von wissenschaftlichem Fehlverhalten nicht reagieren. In dieser Hinsicht kann die eigentliche Frage, inwieweit die Mechanismen zur Selbstkontrolle in der Wissenschaft tragfähig sind, prinzipiell nicht oder nur zu einem Teil beantwortet werden, da diese Mechanismen durch die Verweigerungshaltung vieler Journale gar nicht erst zum Einsatz kommen. So gesehen scheint es auch fraglich, ob zusätzliche Maßnahmen, die auf Grundlage der aus diesem Projekt hervorgegangenen Erfahrungen formuliert werden sollten, die Situation merklich verbessern könnten, da sie den Maßnahmenkatalog, der von Journalen nach wie vor ignoriert werden wird, allenfalls aufblähen. Neben diesen ernüchternden Befunden aufseiten der Journale war auch auf Seiten der sich fehlverhaltenden Autoren wenig Erfreuliches zu festzustellen. In nicht seltenen Fällen ist bei einigen Autorengruppen wissenschaftliches Fehlverhalten tägliche Praxis. Bei der Recherche von Fachartikeln mit manipuliertem Datenmaterial hat es sich fast schon zum Regelfall entwickelt, dass die Durchsicht der Publikationslisten einer einmal auffällig gewordenen Autorengruppe weiteres unlauteres Datenmaterial zutage bringt. Wenn zu den o.a. 207 Fällen alleine ein Autor mit mehr als 30 Fällen beiträgt, so kann man sagen, dass wissenschaftliches Fehl-verhalten stellenweise das Fundament einzelner Karrieren bildet. Flankierend gaben zehn Expert*innen in Interviews Vorschläge zur Verbesserung des Umgangs mit fragwürdigen Publikationen ab. Genannt wurden Beratung, Transparenz, Workshops zur Wissenschaftsethik und zur Identifikation fragwürdiger Inhalte, Open Science-Praktiken (z.B. Prä-Registrierung, Open Access zu Daten, Open Review), verbindliche Richtlinien und Monitoring von Retractions. Bibliotheken wurden besonders als Vermittler von Publikationskompetenz erwähnt. Allerdings wurde von den Expert*innen das gravierende Problem der Nicht-Reaktion der Journale kaum mit Verbesserungsvorschlägen bedacht.The project addressed the central issue of the extent to which existing mechanisms for self-regulation in science are effective in countering scientific misconduct. A total of 207 cases of scientific misconduct were thoroughly documented and reported to the relevant publishers. Only cases with clear indicators of scientific misconduct, such as visibly manipulated data, were reported. Unfortunately, it quickly became apparent that even in these clear cases, the actions taken by journals deviated significantly from the ethical guidelines outlined in their principles regarding scientific misconduct. In many instances, the journals did not even respond to repeated reports of the same case of scientific misconduct. This raises the fundamental question of the viability of self-regulation mechanisms in science, as these mechanisms are often not even utilized due to the resistant attitude of many journals. Thus, it remains questionable whether additional measures formulated based on the findings of this project could significantly improve the situation, as they might merely expand the catalogue of actions that journals continue to disregard. Aside from these disheartening findings regarding journals, there were also discouraging observations concerning authors engaged in misconduct. In some author groups, scientific misconduct has become a routine practice. When researching articles with manipulated data, it has almost become routine to uncover further instances of dubious data in the publication lists of author groups that have previously attracted attention. If a single author contributes to more than 30 out of the aforementioned 207 cases, it is evident that scientific misconduct forms the foundation of certain career trajectories. In parallel, ten experts provided suggestions for improving the handling of questionable publications through interviews. Recommendations included consultation, transparency, work-shops on scientific ethics and content identification, Open Science practices (such as pre-registration, open data access, and open review), binding guidelines, and retraction monitoring. Libraries were particularly highlighted as educators in publication competence. However, the experts scarcely addressed the significant issue of journals' non-responsiveness with proposals for improvement.Deutsche Forschungsgemeinschaft (DFG

Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients’ overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated

A Case Study of the Use of Smart EV Charging for Peak Shaving in Local Area Grids

Electricity storage systems, whether electric vehicles or stationary battery storage systems, stabilize the electricity supply grid with their flexibility and thus drive the energy transition forward. Grid peak power demand has a high impact on the energy bill for commercial electricity consumers. Using battery storage capacities (EVs or stationary battery systems) can help to reduce these peaks, applying peak shaving. This study aims to address the potential of peak shaving using a PV plant and smart unidirectional and bidirectional charging technology for two fleets of electric vehicles and two comparable configurations of stationary battery storage systems on the university campus of Saarland University in Saarbrücken as a case study. Based on an annual measurement of the grid demand power of all consumers on the campus, a simulation study was carried out to compare the peak shaving potential of seven scenarios. For the sake of simplicity, it was assumed that the vehicles are connected to the charging station during working hours and can be charged and discharged within a user-defined range of state of charge. Furthermore, only the electricity costs were included in the profitability analysis; investment and operating costs were not taken into account. Compared to a reference system without battery storage capacities and a PV plant, the overall result is that the peak-shaving potential and the associated reduction in total electricity costs increases with the exclusive use of a PV system (3.2%) via the inclusion of the EV fleet (up to 3.0% for unidirectional smart charging and 8.1% for bidirectional charging) up to a stationary battery storage system (13.3%)

Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling

Clinical islet transplantation is limited by ischemia-induced islet cell death. Recently, it has been reported that the absent in melanoma (AIM)2 inflammasome is upregulated by ischemic cell death due to recognition of aberrant cytoplasmic self-dsDNA. However, it is unknown whether AIM2 determines the outcome of islet transplantation. To investigate this, isolated wild type (WT) and AIM2-deficient (AIM2−/−) islets were exposed to oxygen-glucose deprivation to mimic ischemia, and their viability, endocrine function, and interferon (IFN) signaling were assessed. Moreover, the revascularization and endocrine function of grafted WT and AIM2−/− islets were analyzed in the mouse dorsal skinfold chamber model and the diabetic kidney capsule model. Ischemic WT and AIM2−/− islets did not differ in their viability. However, AIM2−/− islets exhibited a higher protein level of p202, a transcriptional regulator of IFN-β and IFN-γ gene expression. Accordingly, these cytokines were upregulated in AIM2−/− islets, resulting in a suppressed gene expression and secretion of insulin. Moreover, the revascularization of AIM2−/− islet grafts was deteriorated when compared to WT controls. Furthermore, transplantation of AIM2−/− islets in diabetic mice failed to restore physiological blood glucose levels. These findings indicate that AIM2 crucially determines the engraftment and endocrine function of transplanted islets by repressing IFN signaling

Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence

Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicininduced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing

Pharmakokinetisches Modell für Propofol-Sufentanil während Allgemeinanästhesie

Hintergrund: Eine große Herausforderung bei der Durchführung von Allgemeinanästhesien ist der sichere und effektive Umgang mit Medikamenten. Ein Grund hierfür stellt die große interindividuelle Variabilität der Pharmakokinetik von Arzneimitteln dar. Im Rahmen von total intravenöser Anästhesie dosieren Anästhesisten Medikamente u.a. unter Berücksichtigung deren pharmakologischer Eigenschaften, aufgrund von eigener Erfahrung und anhand klinischer Zeichen der Patienten. Eine Echtzeit-Konzentrations-Messung wie bei der balancierten Anästhesie mit Inhalationsanästhetika existiert aktuell nicht oder ist nur durch hohen Aufwand im Labor möglich. Mittels Target-Controlled-Infusion (TCI) ist es allerdings möglich Plasmakonzentrationen von Medikamenten anzusteuern, die auf Grundlage pharmakokinetischer Modelle berechnet wurden. Es gibt bereits eine Vielzahl von pharmakokinetischen Modellen für Propofol und für Sufentanil. Eine populationspharmakokinetische Untersuchung, die Wechselwirkungen zwischen beiden Medikamenten herausstellen konnte, existiert bisher nicht. Ziel dieser Arbeit sollte die Berechnung eines populationsbasierten pharmakokinetischen Models von Propofol und Sufentanil sein. Der Einfluss von Covariaten sollte beschrieben und mögliche Interaktionen zwischen den beiden Medikamenten eruiert werden, um daraus adäquate Dosierungsempfehlungen ableiten zu können. Methoden: In dieser prospektiven Studie führten wir eine Allgemeinanästhesie mit Propofol und Sufentanil bei 35 Patienten im Alter von 35 - 88 Jahren durch. Die Propofolgabe erfolgte als TCI mit dem Parametersatz des Marsh-Modells. Sufentanil wurde bolusweise nach Bedarf des Patienten dosiert. Während der Narkose wurden arterielle Blutproben entnommen und die Plasmakonzentrationen von Propofol und Sufentanil mittels Hochleistungsflüssigkeitschromatographie (HPLC) ermittelt. In die Analyse wurden 341 Blutproben eingeschlossen. Die Berechnung des pharmakokinetischen Modells wurde anschließend mit dem Software-Programm NONMEM durchgeführt. Ergebnisse: Die erhobenen Daten konnten sowohl für Propofol, als auch für Sufentanil an ein 3-Kompartiment-Modell angepasst werden. Als relevante Covariaten im Propofol-Modell wurden Alter > 60 Jahren, Körpergröße und Quotient aus Herzfrequenz und diastolischem Blutdruck auf die Eliminationsclearance Clelim(Propofol) sowie Körpergröße auf das zentrale Kompartiment V1 identifiziert. In das Sufentanil-Modell konnte die Covariate Alter > 60 Jahren mit Einfluss auf die Eliminationsclearance Clelim(Sufentanil) integriert werden. Ebenso zeigte sich eine Interaktion von Propofol und Sufentanil auf pharmakokinetischer Ebene. So ließ sich eine Reduktion der Eliminationsclearance Clelim(Sufentanil) von Sufentanil mit Zunahme der Propofolkonzentration im zentralen Kompartiment V1 des Propofol-Modells feststellen. Die Modellbewertung erfolgte anhand der Objektivierungsfunktion und Goodness-of-fit Plots. Es zeigte sich eine gute Korrelation der gemessenen und der durch das Modell vorhergesagten Plasmakonzentrationen mit einer Präzision von 15,9% für das Propofol-Modell und 18,9% für das Sufentanil-Modell. Zusammenfassung: Bei der Komedikation mit Propofol und Sufentanil müssen pharmakokinetische Wechselwirkungen berücksichtigt werden, die zu einer Dosisanpassung während der Narkose führen. Bei älteren Patienten ist eine Dosisreduktion von Propofol und Sufentanil sinnvoll, um Nebenwirkungen zu vermeiden.Background: A major challenge in the performance of general anesthesia is the safe and effective handling of medication. One reason for this is the large inter-individual variability of the pharmacokinetics of drugs. In the context of total intravenous anesthesia, anesthesiologists dose medications on the one hand taking into account pharmacological properties and on the other hand on the basis of their own experience and of clinical signs of the patients. A realtime concentration measurement as with balanced anesthesia with inhalation anesthetics does not currently exist or is only possible through high effort in the laboratory. By means of targetcontrolled infusion (TCI), however, it is possible to control plasma concentrations of drugs that have been calculated on the basis of pharmacokinetic models. There are already a variety of pharmacokinetic models for propofol and for sufentanil. A population pharmacokinetic study that is able to identify interactions between the two drugs does not yet exist. The aim of this work should be the calculation of a population-based pharmacokinetic model of propofol and sufentanil. The influence of covariates should be described and possible interactions between the two drugs should be determined in order to be able to derive adequate dosage recommendations. Methods: In this prospective study, we performed general anesthesia with propofol and sufentanil in 35 patients aged 35 - 88 years. Propofol administration was carried out as TCI with the parameter set of the Marsh model. Sufentanil was dosed bolus-wise as required by the patient. During anesthesia, arterial blood samples were taken and plasma concentrations of propofol and sufentanil were determined using High-performance-liquid-chromatographie (HPLC). 341 blood samples were included in the analysis. The calculation of the pharmacokinetic model was then carried out with the software program NONMEM. Results: The collected data could be adapted to a 3-compartment model for both propofol and sufentanil. Relevant covariates in the propofol model were identified as age > 60 years, height and quotient of heart rate and diastolic blood pressure to the elimination clearance Clelim(Propofol) and height to the central compartment V1. In the sufentanil model, the covariate age > 60 years with influence on the elimination clearance Clelim(Sufentanil) could be integrated. There was also an interaction of propofol and sufentanil at the pharmacokinetic level. Thus, a reduction in the elimination clearance Clelim(Sufentanil) of sufentanil with an increase in the propofol concentration in the central compartment V1 of the propofol model could be observed. The model evaluation was based on the objective function and goodness-of-fit plots. There is a good correlation of the plasma concentrations measured and the plasma concentrations predicted by the model with a precision of 15.9% for the propofol model and 18.9% for the sufentanil model. Summary: In comedication with propofol and sufentanil, pharmacokinetic interactions must be taken into account, that leading to dose adjustment during anesthesia. In elderly patients, a dose reduction of propofol and sufentanil is useful to avoid side effects

Frozen Stored Teeth : Autogenous Dentin as an Alternative Augmentation Material in Dentistry

Tooth Shell Technique (TST) with the use of autologous dentin has proven to be a suitable method of grafting in the context of lateral ridge augmentation. This present feasibility study aimed to retrospectively evaluate the preservation by lyophilization of processed dentin. Thus, the frozen stored processed dentin matrix (FST: 19 patients with 26 implants) was re-examined with that of processed teeth used immediately after extraction (IUT: 23 patients with 32 implants). Parameters of biological complications, horizontal hard tissue loss, osseointegration, and buccal lamella integrity were used for evaluation. For complications, the observation period was 5 months. Only one graft was lost (IUT group). In the area of minor complications, without the loss of an implant or augmentation, there were two cases of wound dehiscence and one case with inflammation and suppuration (IUT: n = 3, FST: n = 0). Osseointegration and integrity of the buccal lamella were present in all implants without exception. Statistically, there was no difference between the groups studied for the mean resorption of the crestal width and the buccal lamella. Results of this study show that prepared autologous dentin preserved with a conventional freezer had no disadvantage compared to immediately use autologous dentin in terms of complications and graft resorption in the context of TST