Comparison of the shaping ability of RaCe, FlexMaster, and ProFile nickel-titanium instruments in severely curved root canals

This in vitro study compared the shaping ability of RaCe, FlexMaster, and ProFile rotary nickel-titanium instruments in severely curved root canals of extracted teeth. Sixty maxillary molars with curvatures ranging from 25° to 65° were embedded in a muffle system and portioned into five horizontal sections (thickness 1.2 mm), starting from the apex. Canals were divided into three groups (n = 20, each) and were prepared with RaCe, FlexMaster, or ProFile rotary nickel-titanium instruments and the TriAuto ZX handpiece using a crown-down preparation technique. We evaluated the difference between pre- and postoperative root canal cross-sections, loss of working length, instrument failure, and preparation time. The root canal area before and after the intervention was determined using an area-measuring software. The data were analyzed statistically using a one-way ANOVA followed by a Kruskal-Wallis multiple-comparison Z-value test. Specimens treated with FlexMaster showed the greatest change from preoperative cross-sections, followed by RaCe and ProFile. The cross-sectional changes induced by RaCe and FlexMaster preparation differed significantly from those produced by ProFile. Loss of working length, instrument failure, and preparation time did not differ significantly between the groups. Root canal preparation with the three instruments did not lead to any significant alteration of the original root anatomy or working length. Thus, we conclude that RaCe, FlexMaster, and ProFile instruments are of comparable efficiency and usefulness in the preparation of severely curved root canals

Music-evoked incidental happiness modulates probability weighting during risky lottery choices

We often make decisions with uncertain consequences. The outcomes of the choices we make are usually not perfectly predictable but probabilistic, and the probabilities can be known or unknown. Probability judgments, i.e., the assessment of unknown probabilities, can be influenced by evoked emotional states. This suggests that also the weighting of known probabilities in decision making under risk might be influenced by incidental emotions, i.e., emotions unrelated to the judgments and decisions at issue. Probability weighting describes the transformation of probabilities into subjective decision weights for outcomes and is one of the central components of cumulative prospect theory (CPT) that determine risk attitudes. We hypothesized that music-evoked emotions would modulate risk attitudes in the gain domain and in particular probability weighting. Our experiment featured a within-subject design consisting of four conditions in separate sessions. In each condition, the 41 participants listened to a different kind of music-happy, sad, or no music, or sequences of random tones-and performed a repeated pairwise lottery choice task. We found that participants chose the riskier lotteries significantly more often in the "happy" than in the "sad" and "random tones" conditions. Via structural regressions based on CPT, we found that the observed changes in participants' choices can be attributed to changes in the elevation parameter of the probability weighting function: in the "happy" condition, participants showed significantly higher decision weights associated with the larger payoffs than in the "sad" and "random tones" conditions. Moreover, elevation correlated positively with self-reported music-evoked happiness. Thus, our experimental results provide evidence in favor of a causal effect of incidental happiness on risk attitudes that can be explained by changes in probability weighting

Evaluating differently tutored groups in problem-based learning in a German dental curriculum: a mixed methods study

Background: It is still unclear to what extent the PBL tutor affects learning in PBL-sessions. This mixed-methods study (Part 1 and 2) evaluated the effects of facilitative (f) versus non-facilitative (nf) tutoring roles on knowledge-gain and group functioning in the field of endodontics. Methods: Part 1 was a quantitative assessment of tutor effectiveness within a prospective, experimental, single-blind, stratified, randomized, two-group intervention study. Participants attended PBL in the context of a hybrid curriculum. A validated questionnaire was used and knowledge assessments were conducted before and after the intervention. External observers rated tutor performance. Part 2 was a qualitative assessment of tutor effectiveness and consisted of semi-structured expert interviews with tutors and focus group discussions with students. Results: Part 1: f tutors obtained significantly higher scores than nf tutors with respect to learning motivation and tutor effectiveness (p ≤ 0.05). nf tuition resulted in a slightly larger knowledge gain (p = 0.08). External observers documented a significantly higher activity among facilitative tutors compared to non-facilitative tutors. Part 2: Tutors found the f role easier although this led to a less autonomous working climate. The students rated f tutoring as positive in all cases. Conclusions: With respect to PBL-group performance, students felt that groups guided in a non-facilitative fashion exhibited a higher level of independence and autonomy, especially with increasing PBL experience. In addition, students reported that more preparation was necessary for sessions guided by a non-facilitative tutor. Tutors were able to modify their role and influence group processes in a controlled manner. Results are useful for future “Train-the-Teacher” sessions

Patient Preferences Regarding Chemotherapy in Metastatic Breast Cancer—A Conjoint Analysis for Common Taxanes

Background: The purpose of this investigation was to explore patient perception regarding the importance of efficacy, toxicity, and logistics in the choice of regimen of taxane-based chemotherapy (CHT) for patients with metastatic breast cancer (MBC).Methods: This dual-center study analyzed data of 100 women diagnosed with MBC, who were asked for their preferences regarding chemotherapy by means of conjoint analysis. Included attributes were progression free survival (PFS), application form, time and frequency, need of premedication, risk of alopecia, fatigue, febrile neutropenia, and neuropathy. Furthermore, participants completed a questionnaire about their personal and medical history. Regression analyses were performed to identify factors that influence patient preference in terms of specific treatment choice.Results: Of 8 attributes, severe neutropenia was top priority for the majority of patients, followed by alopecia, neuropathy and PFS. When combining these patient preferences and the results of the questionnaire, patients' age as, well as, relationship status had significant impact on the importance of PFS. Moreover, longer travel time to the treatment center was significantly associated with preferences regarding PFS. Ranking by combination of respective part-worth values demonstrated nab-paclitaxel to be favored over paclitaxel and docetaxel.Conclusion: Side effects of CHT and PFS prove to be critical factors for patients affecting choice of treatment in MBC with severe neutropenia being top priority, followed by alopecia, neuropathy, and PFS. Age, commute time, and relationship status were identified as significant determinants of patient preference. Total utility calculation by combination of part-worth values ranked nab-paclitaxel as the most preferable taxane

Pulmonary Hypertension in Patients with Chronic Kidney Disease on Dialysis and without Dialysis: Results of the PEPPER-Study

Pulmonary hypertension (PH) is common in patients with dialysis-dependent chronic kidney disease and is an independent predictor of mortality. However, specific hemodynamics of the pulmonary circulation, changes induced by hemodialysis and characterization into pre- or postcapillary PH have not been evaluated in patients with chronic kidney disease. We assessed consecutive patients with end-stage chronic kidney disease in WHO FC≥II with dyspnea unexplained by other causes on hemodialysis (group 1, n = 31) or without dialysis (group 2, n = 31) using right heart catheterization (RHC). In group 1, RHC was performed before and after dialysis. In end-stage chronic kidney disease, prevalence of precapillary PH was 13% (4/31), and postcapillary PH was discovered in 65% (20/31). All four cases of precapillary PH were unmasked after dialysis. In group 2, two cases of precapillary PH were detected (6%), and postcapillary PH was diagnosed in 22 cases (71%). This is the first study examining a large cohort of patients with chronic kidney disease invasively by RHC for the prevalence of PH. The prevalence of precapillary PH was 13% in patients with end-stage kidney disease. That suggests careful screening for precapillary PH in this selected patient population. RHC should be performed after hemodialysis

Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes

AbstractThis article presents detailed purification procedures for the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1) and BRD4(1) in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC) and by differential scanning fluorimetry (DSF) as well as structural characterizations of BRD4(1) inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T). These data have been reported previously and are discussed in more detail elsewhere [1,2]

Wnt/beta-catenin signaling controls development of the blood–brain barrier

The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown

Riboflavin synthase of Schizosaccharomyces pombe. Protein dynamics revealed by (19)F NMR protein perturbation experiments

BACKGROUND: Riboflavin synthase catalyzes the transformation of 6,7-dimethyl-8-ribityllumazine into riboflavin in the last step of the riboflavin biosynthetic pathway. Gram-negative bacteria and certain yeasts are unable to incorporate riboflavin from the environment and are therefore absolutely dependent on endogenous synthesis of the vitamin. Riboflavin synthase is therefore a potential target for the development of antiinfective drugs. RESULTS: A cDNA sequence from Schizosaccharomyces pombe comprising a hypothetical open reading frame with similarity to riboflavin synthase of Escherichia coli was expressed in a recombinant E. coli strain. The recombinant protein is a homotrimer of 23 kDa subunits as shown by sedimentation equilibrium centrifugation. The protein sediments at an apparent velocity of 4.1 S at 20°C. The amino acid sequence is characterized by internal sequence similarity indicating two similar folding domains per subunit. The enzyme catalyzes the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine at a rate of 158 nmol mg(-1 )min(-1 )with an apparent K(M )of 5.7 microM. (19)F NMR protein perturbation experiments using fluorine-substituted intermediate analogs show multiple signals indicating that a given ligand can be bound in at least 4 different states. (19)F NMR signals of enzyme-bound intermediate analogs were assigned to ligands bound by the N-terminal respectively C-terminal folding domain on basis of NMR studies with mutant proteins. CONCLUSION: Riboflavin synthase of Schizosaccharomyces pombe is a trimer of identical 23-kDa subunits. The primary structure is characterized by considerable similarity of the C-terminal and N-terminal parts. Riboflavin synthase catalyzes a mechanistically complex dismutation of 6,7-dimethyl-8-ribityllumazine affording riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. The (19)F NMR data suggest large scale dynamic mobility in the trimeric protein which may play an important role in the reaction mechanism