Supramolecular ligands for 14-3-3 proteins

Im Rahmen der vorliegenden Arbeit sollten supramolekular-wirkende 14-3-3-Inhibitoren entwickelt und untersucht werden. Da 14-3-3-Proteine funktionale Dimere bilden, sollten hierzu bivalente Liganden synthetisiert werden, welche zeitgleich beide Bindungstaschen besetzen können und somit affiner als monovalente Inhibitoren binden sollten. Zur Bindung an die 14-3-3-Phosphoserin/-threonin-Bindungstasche sollte dabei das früher etablierte Phosphophenolether-Bindungsmotiv verwendet werden. Innerhalb dieser Arbeit konnten erfolgreich fünf verschiedene, potentiell bivalent-bindende Phosphophenolether-Derivate (Biv1 bis Biv5) hergestellt und untersucht werden. Für alle synthetisierten bivalenten Moleküle konnte dann mittels FP-Messung eine Wechselwirkung mit dem 14-3-3-Protein nachgewiesen werden. Ein weiterer Aspekt dieser Arbeit war die Entwicklung von Isoform-spezifischen Inhibitoren. Hierzu wurden bioreaktive Phosphophenolether-Verbindungen entwickelt, die aufgrund ihrer bioreaktiven Gruppe speziell mit der σ-Isoform interagieren sollten, da nur diese Isoform über ein Cystein und damit eine Thiol-Gruppe in der Nähe der Phosphophenolether-Bindungstasche verfügt.Aim of this work was the development and investigation of supramolecular inhibitors of 14-3-3 proteins. Due to the dimeric nature of 14-3-3 proteins, a particular focus was thereby set on the development of bivalent ligands which simultaneously may occupy both substrate binding pockets and thus should display better binding affinities than monovalent ligands. For targeting of the phosphoserine/threonine site, the previously established phosphophenol ether motif should thereby be used. Within this work, five different, potentially bivalent-binding phosphophenol ether derivatives (Biv1 to Biv5) were prepared and investigated. All newly synthesized bivalent molecules were subsequently characterized by FP-based affinity measurements that revealed that all compounds bound the 14-3-3 proteins, however with strongly different affinities. Another aspect of this work was the development of 14-3-3 isoform-specific inhibitors. For this purpose, bioreactive phosphophenol ethers were developed, which due to their bioreactive group were envisaged to display 14-3-3σ specificity as only this isoform harbors a cysteine residue in vicinity of the phosphophenol ether binding pocket

The Assessment of Knowledge, Behaviors, and Anxiety Levels of the Orthodontists about COVID-19 Pandemic

Objective:A new viral disease called Coronavirus disease-19 (COVID-19) affected the whole world because of its characteristics of spreading rapidly via respiratory droplets and aerosol. As one of the most aerosol-generating occupations, dentists are at high risk and are recommended to treat emergency cases only. We aimed to assess the general knowledge, emergencies, personal precautions, and avoided behaviors among the orthodontists and also their anxiety levels, during COVID-19.Methods:A survey research, including demographic information, general knowledge about COVID-19, treatment strategies, protective measures, and Generalized Anxiety Disorder (GAD) 7 test, was conducted via a web-based questionnaire (1 open-ended and 26 closed-ended questions). A total of 215 orthodontists older than 20 years of age and practicing in different regions of Turkey were included in this study. The answers received within the first 10 days were included.Results:Most of the orthodontists were aware of COVID-19 symptoms and transmission routes (n=159 and n=183, respectively). Almost all of them treated only emergency cases (n=209). Orthodontic emergencies were reported mostly as injury due to band/bracket failure, soft/hard tissue trauma, and problems in retention appliances (n=197, n=186, and n=81, respectively). The participants also avoided aerosol-generating procedures and used transmission-based protective equipment. The prevalence of GAD was 16.7% during COVID-19, and there was no statistically significant difference when it was stratified by gender, age, city, and COVID-19 related questions (p>0.05).Conclusion:The orthodontists followed the guidelines and took protective measures during COVID-19, and the majority had subthreshold anxiety levels

Assessment of the Diagnostic Skills of General Dentists in Different Types of Orthodontic Malocclusions

Objective: One of the biggest problems in publicly funded dental clinics is the patient waiting list. The appropriate referral plays a key role in avoiding an increase in the number of patients on this waiting list. This study aimed to assess general dentists’ diagnostic skills and approaches for different malocclusions.Methods: A questionnaire was prepared using photos of 8 patients previously treated for different malocclusions. One hundred twenty general dentists (83 female, mean age: 24 ± 1.18 years; 37 male, mean age: 24 ± 1.95 years) participated in the survey and were asked to decide whether the patient needed orthodontic treatment or orthognathic surgery, and to provide the reason for surgery (irregular teeth, or both unesthetic profile and irregular teeth), and the cause of the unesthetic profile (mandibular protrusion, mandibular retrusion, maxillary protrusion, maxillary retrusion).Results: The answers suggesting the need for orthodontic treatment were significantly higher for all malocclusions except for the Class II camouflage case. Of the Class III cases, the general dentists chose orthognathic surgery for both surgery and facemask cases (93.1%, 66.4% respectively). For the severe open bite case, orthognathic surgery was chosen with a ratio of 81.2%, and orthognathic surgery was decided as not necessary for the mild open bite case (74.8%). Among the surgery cases, mandibular retrusion for the Class II case (94.6%), mandibular protrusion for Class III case (95.4%), and maxillary retrusion for the severe open bite case (44.6%) were the maximum reported reasons.Conclusion: The distinction between camouflage and surgical treatment was better made by dentists in Class II and open bite cases than in Class III cases

Serum testosterone levels and Colonic Diverticula

Background: Elderly men have a high risk of metabolic syndrome, including an increased risk of obesity. Whether low testosterone is associated with diverticular disease of the colon (DDC) risk independent of metabolic co-factors is not clear. Aim: This study was conducted this study to reveal the possible link between serum testosterone levels and colonic diverticula. Methods: This study was conducted between May 2018 and December 2018, total 208 subjects were enrolled for the study at a university hospital, Turkey. At total, 85 men with DDC were enrolled for the study. DDC was defined by non-contrast CT scan with colonoscopic examination. Control group (123 subjects without DDC; the mean age was 54.5 ±14.5) were selected from otherwise healthy men. Results: Of the 85 men with DDC, the mean age was 60.8 ± 13.5 years. Lower levels of total testosterone were associated with a 25% increased odds of prevalent DDC on adjusted analyses. Importantly, lower levels of total testosterone remained strongly associated with prevalent DDC, even in men with normal glucose levels (p=0.01). Conclusion: Decreasing levels of total testosterone, even within normal range, are independently associated with DDC in elderly age. Androgen deficiency may have an important role in the development of DDC in men and provide a potential novel target for DDC prevention

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

İngilizce ders kitaplarında cinsiyet temsili : karşılaştırmalı bir çalışma

In all educational institutions ELT coursebooks are used as a guide to teach the language. However, the role of a coursebook as an agent of socialization and its effect on the development of gender roles is usually underestimated. Gender biased coursebooks might affect the learners in a negative way in the process of gender socialization. Most coursebook writers revise the first editions of the coursebooks in order to modernize them and to meet the needs of the learners in a changing world. The aim of this thesis is to investigate whether writers and publishers take the gender issue into consideration while they are revising the coursebooks. In order to address this issue, three recently revised English language coursebooks were compared with their first editions. To be able to compare the coursebooks, their contents were analyzed. Six operating areas of gender stereotypes were set as the categories of the content analysis; presence of female and male characters in the coursebooks, the number of characters represented as family members, distribution of occupational activities, division of household activities, variety of leisure activities and the adjectives used to describe each gender. Throughout the whole study it was observed that the representations of female and male characters in the first editions were closer to the stereotypical representations. By contrast, in the last editions the representations of the genders have ideally become more balanced in all investigated categories of gender stereotypes.M.S. - Master of Scienc

Students' understanding of matter: The effect of reasoning ability and grade level

This study aims at investigating the effect of grade level on students' achievement in matter concept and reasoning abilities, when their test anxiety was controlled. The data was collected from 8th, 10th and 11th grade students by the administration of The Matter Concept Test, Test of Logical Thinking, and the Motivated Strategies for Learning Questionnaire. The results revealed that there was a significant effect of grade level on students' achievement in favor of 11th grade students and the linear combination of reasoning abilities was significantly related to students' achievement. In the Matter Concept Test, the 10th graders did better than 8th graders and the 11th graders did better than either. The only exception to this general observation was the 8th graders' better performance on a small number of questions, which related to topics that were taught and nationally examined in the 8th grade. It seems likely, therefore, that the more chemistry a student is taught the better he/she is likely to be, except that if a topic is examined while it is reasonably fresh in a student's mind the results are likely to be better than if the test is carried out 2-3 years later. © The Royal Society of Chemistry

Determination of Antidepressant Drug Use Among Inpatients in Medical and Surgical Clinics

WOS: 000462818200001Objective: This cross-sectional study was performed to determine antidepressant drug use among inpatients in medical and surgical clinics. Methods: The study sample consisted of 478 inpatients from a state hospital, between December 1, 2015 and January 1, 2016. The information form was applied to the patients. Number and percentage distribution were used for data analysis. Results: Of the 478 patients, 34.5% had visited a psychiatrist once in their lifetime, 13.6% were diagnosed with depression, and 13.8% did not know the diagnosis of mental disease; 32.2% were suggested medication by their doctor, 16.7% did not know the name of this medication, and 13.2% stated that the suggested drug was antidepressant. Moreover, 24.9% of the patients were known to use antidepressant at least once in their lifetime, and 16.3% were still using antidepressants. Among patients using antidepressants, 32% continued using this drug upon doctor's recommendation and 13.6% continued with the diagnosis of depression. Conclusion: It might be concluded that one-fourth of the patients used antidepressant once in their lifetime; more than one-half of these patients were still using antidepressants, and most of them were using the drug upon doctor's recommendation without any knowledge about antidepressants

Soft tissue evaluation after maxillary protraction with RPE or with the ALT-RAMEC protocol A controlled 3D study

Purpose To evaluate soft tissue changes following maxillary protraction with different expansion protocols using three-dimensional (3D) stereophotogrammetry. Methods Pretreatment (T0) and postprotraction (T1) stereophotogrammetry and lateral cephalometric images of skeletal class III patients were included in this retrospective study. In all, 32 patients were treated either with a combination of rapid palatal expansion and facemask (RPE/FM; n = 16; mean age: 9.94 +/- 0.68 years) or with alternate rapid maxillary expansion and constriction together with a facemask (Alt-RAMEC/FM; n = 16; mean age: 9.74 +/- 1.35 years). As a control group 16 untreated patients were recruited (mean age: 9.46 +/- 0.8 years). For superimpositioning of the 3D images taken at T0 and T1, the face was divided into defined regions and 3D and differences between the groups were evaluated using 3-matic software (Materialise Europe, Leuven, Belgium). Cephalometric analyses were also performed. Results While the increases in the cephalometric parameters SNA and ANB were significantly greater in the treatment groups, the value for SNB also increased in the control group (p < 0.05). The results of the stereophotogrammetry analyses demonstrated that the mean changes in the RPE/FM and in the Alt-RAMEC/FM groups were significantly different for the midface compared to the control group (0.33 +/- 0.26 mm, 0.3 +/- 0.31 mm, 0.1 +/- 0.18 mm). The maximum positive, negative, and mean changes were also significantly different between the treatment and control groups for the upper lip (p < 0.05). For the lower lip and the chin significant backward movements in the RPE/FM as well as in the Alt-RAMEC/FM group (-1.06 +/- 1.26 mm, -0.68 +/- 0.45 mm) were observed, while the control group (0.09 +/- 0.53 mm) presented changes in the opposite direction. Regarding soft tissue changes, no significant differences were found between the RPE/FM and Alt-RAMEC/FM groups. Conclusion Both treatment protocols improved the soft tissue profile due to a forward movement of the midface and the upper lip, and a backward movement of the lower lip and chin, compared to the control group