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Naphthothiophenes were prepared from commercially available 2,3-dibromothiophenes in two steps by one-pot Suzuki/Sonogashira or Sonogashira/Suzuki coupling reactions, followed by intramolecular alkyne-carbonyl-metathesis reactions. The final cyclization reaction proceeds in the presence of

In Germany, a curriculum in special care dentistry (SCD) is not mandatory. As a result, very little is known about dental students' attitudes toward interacting with people with disability (PwD). The study´s aim was to assess this among dental students at Witten/Herdecke University (UW/H).In the academic years 2016-2017 to 2020-2021, dental students in the 7th semester (UW/H) were asked to complete a self-assessment questionnaire. Prior to its start, the study had obtained a positive vote from the ethics committee of the UW/H (#174/2016).Out of 199 students 166 persons on average 24.5 years old completed the questionnaire. Nearly all participants had already had previous experience with PwD in various domains of life prior to dental school (89.2%). Three-quarters indicated not having reservations about interacting with PwD. The proportion of persons without previous experience in interacting with a PwD was almost twice as high in the group with reservation (16.2%) as it was in the group without reservation (8.7%). Almost all surveyed students (92.8%) affirmed that they would like to learn more on the topic of "Professional Interaction with PwD."Most of the respondents did not have reservations about interacting with PwD. Almost all the participants indicated a high level of interest in topics related to SCD. Also, the authors like to encourage the curriculum committees of dental schools at other universities to integrate courses on SCD, based on the iADH recommendations, into their dental curricula.

Dibenzocycloheptanones (dibenzotropones) were prepared by Bronsted acid mediated intramolecular alkyne-carbonyl metathesis (ACM) reactions. The cyclization precursors are readily available by Sonogashira reaction of 2-bromobenzoyl chloride with terminal alkynes, followed by Suzuki reactions with benzaldehydes. The ACM reactions are highly modular and atom economic and allow for the construction of two regioisomeric series of dibenzotropones.

Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64-95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95->99 % and up to 98 % yield.

Many digital interventions rely on the participation of their users to have a positive impact. In various areas it can be observed that the use of digital interventions is often reduced or fully discontinued by the users after a short period of time. This is seen as one of the main factors that can limit the effectiveness of digital interventions. In this context, the concept of adherence to digital interventions is becoming increasingly important. Adherence to digital interventions is roughly defined as "the degree to which the user followed the program as it was designed," which can also be paraphrased as "intended use" or "use as it is designed." However, both the theoretical-conceptual and practical discussions regarding adherence to digital interventions still receive too little attention.The aim of this narrative review article is to shed more light on the concept of adherence to digital interventions and to distinguish it from related concepts. It also discusses the methods and metrics that can be used to operationalize adherence and the predictors that positively influence adherence. Finally, needs for action to better address adherence are considered critically.Viele digitale Interventionen sind auf die Mitwirkung ihrer Nutzer*innen angewiesen, damit sie eine positive Wirkung erzielen können. In verschiedenen Bereichen ist zu beobachten, dass die Anwendung digitaler Interventionen durch Nutzer*innen oftmals nach einer kurzen Zeit reduziert oder in Gänze eingestellt wird. Dies wird als einer der wesentlichen Faktoren angesehen, der die Wirksamkeit digitaler Interventionen einschränken kann. In diesem Zusammenhang gewinnt das Konzept der Adhärenz (Einhalten therapeutischer Vorgaben) bei digitalen Interventionen zunehmend an Bedeutung. Definiert wird Adhärenz bei digitalen Interventionen etwa als „the degree to which the user followed the program as it was designed“ („Ausmaß, in dem die Nutzer*innen die Software so verwenden, wie sie konzipiert wurde“). Dies wird auch oftmals mit „intended use“ oder „use as it is designed“ umschrieben („bestimmungsgemäße Verwendung“ bzw. „Verwendung, wie es konzipiert wurde“). Jedoch finden sowohl die theoretisch-konzeptionelle als auch die praktische Auseinandersetzung hinsichtlich der Adhärenz bei digitalen Interventionen noch eine zu geringe Berücksichtigung in der Forschung.Ziel dieses narrativen Übersichtsartikels ist es, das Konzept der Adhärenz bei digitalen Interventionen näher zu beleuchten und von verwandten Konzepten abzugrenzen. Zudem wird diskutiert, mit welchen Methoden und Messgrößen die Adhärenz operationalisiert werden kann und welche Prädiktoren die Adhärenz positiv beeinflussen. Weiterhin wird auf die Dosis-Wirkungs-Beziehung bei der Anwendung digitaler Interventionen eingegangen und auf Faktoren, die die Adhärenz positiv beeinflussen können. Abgeschlossen wird mit einer ethischen Betrachtung der Thematik.

A series of 5,7,9-substituted 2-azapyrenes were synthesized for the first time. The synthesis relies on Brønsted acid promoted benzannulation of alkyne precursors prepared by palladium-catalyzed cross-coupling reactions. The synthetic strategy is efficient and the scope covers a variety of functional groups. The electrochemical behavior and photophysical properties of the products were investigated by UV-vis and fluorescence spectroscopy, cyclic voltammetry, and DFT calculations.

A straightforward, site-selective arylation of the bis(triflate) of estrone by Suzuki–Miyaura reactions has been developed. Monoarylation occurs selectively at the D-ring with good to excellent yield. Such products were exemplarily employed for the synthesis of estrones containing two different aryl substituents.

Background: Paediatric palliative care (PPC) is a noncurative approach to the care of children and adolescents with life-limiting and life-threatening illnesses. Electronic medical records (EMRs) play an important role in documenting such complex processes. Despite their benefits, they can introduce unintended consequences if future users are not involved in their development. Aim: The aim of this study was to evaluate the acceptance of a novel module for nursing documentation by nurses working in the context of PPC. Methods: An observational study employing concurrent think-aloud and semi-structured qualitative interviews were conducted with 11 nurses working in PPC. Based on the main determinants of the unified theory of acceptance and use of technology (UTAUT), data were analysed using qualitative content analysis. Results: The main determinants of UTAUT were found to potentially influence acceptance of the novel module. Participants perceived the module to be self-explanatory and intuitive. Some adaptations, such as the reduction of fragmentation in the display, the optimization of confusing mouseover fields, and the use of familiar nursing terminology, are reasonable ways of increasing software adoption. Conclusions: After adaptation of the modules based on the results, further evaluation with the participation of future users is required.

Background: Electronic medical records (EMRs) play a key role in improving documentation and quality of care in paediatric palliative care (PPC). Inadequate EMR design can cause incorrect prescription and administration of medications. Due to the fact of complex diseases and the resulting high level of medical complexity, patients in PPC are vulnerable to medication errors. Consequently, involving users in the development process is important. Therefore, the aim of this study was to evaluate the acceptance of a medication module from the perspective of potential users in PPC and to involve them in the development process. Methods: A qualitative observational study was conducted with 10 nurses and four physicians using a concurrent think-aloud protocol and semi-structured qualitative interviews. A qualitative content analysis was applied based on a unified theory of acceptance and use of technology. Results: Requirements from the user’s perspective could be identified as possible influences on acceptance and actual use. Requirements were grouped into the categories “performance expectancies” and “effort expectancies”. Conclusions: The results serve as a basis for further development. Attention should be given to the reduction of display fragmentation, as it decreases cognitive load. Further approaches to evaluation should be taken.

Pediatric palliative care (PPC) patients require years of care across professions and sectors. Sharing treatment-related information and communicating among different PPC professionals is critical to ensure good quality of care. In Germany, this communication is mostly paper-based and prone to errors. Therefore, an electronic cross-facility health record (ECHR) was participatorily designed with users, wherein information can be shared and PPC professionals can communicate with each other. As this form of electronic health record differs from existing models in Germany, there is a need for successful implementation to ensure a positive impact. Therefore, the facilitators and barriers to the implementation of ECHR in PPC were examined. Using the consolidated framework for implementation research (CFIR), transcripts of 32 interviews, 3 focus groups, and 20 think-aloud studies with PPC professionals were analyzed. CFIR indicated that the ECHR-design was viewed positively by users and can be a facilitator for implementation. Barriers exist, mainly due to the fact that the implementation is not planned, the use of the ECHR involves effort, costs are not covered, and all users must be motivated to use the ECHR for functionality. CFIR helps uncover the crux of the issues that need to be considered when planning ECHR implementation to improve care in PPC.

1,8-Naphthyridines are previously showed various biological activity and have been employed in supramolecular chemistry. We herein report the synthesis of formerly unknown 3,6-dibromo-2,7-dichlorotetrahaphthyridine and its employment in by Palladium catalysed Suzuki-Miyaura reaction. Synthesized 2,3,6,7-tetraarylnaphthtyridines have been obtained in generally good to excellent yields. The impact of donor- and acceptor substituents as well as the influence of acid on the optical properties have been studied by steady-state UV/Vis- and fluorescence spectroscopy and further analysed by cyclovoltammetry and DFT-calculations.

The economic value of the oceans and maritime industry is strongly gaining in importance. As the oceans are very large and particularly sensitive ecosystems, which need to be preserved, a balance between the use and the protection of the seas has to be found. On this issue, the paper presents some thoughts starting with a brief analysis of what to understand by maritime industry which is labeled as blue economy, and a recapitulation of the main threats for the marine environment, caused by blue economy. After that, some noteworthy prerequisites and criteria for finding a sound balance between the use and the protection of the seas will be highlighted, especially the need for sustainable ocean governance is put to discussion.

Sonogashira reactions of steroids have been studied. The reaction of α-estron-16-methylidenyloxy triflate with various alkynes afforded novel alkynylvinylidene steroids. The reactions proceeded in good to quantitative yields, with excellent E-selectivity and with a broad synthetic scope.

Over expression of nucleotide pyrophosphatase (NPPs) activity is associated with chondrocalcinosis, osteoarthritis, type 2 diabetes, neurodegenerative diseases, allergies and cancer metastasis. The potential of NPPs inhibitors as therapeutic agents, and the scarceness of their structure–activity relationship, encouraged us to develop new NPP inhibitors. Specifically, 2-bromo-7-methyl-5-oxo-5H-1,3,4-thiadiazolopyrimidine and its corresponding 6-fluoro derivatives were synthesized via a Suzuki–Miyaura reaction. The cross-coupling reaction with different arylboronic acids gave desired coupling products in good to excellent yields and showed wide functional group tolerance. Furthermore, all compounds were investigated for their potential to inhibit two families of ecto-nucleotidases, i.e. nucleoside triphosphate diphosphohydrolases (NTPDase) and NPPs. Interestingly, our compounds were identified as selective inhibitors of NPPs. Among derivatives 5a–5i, compound 5i (IC50 ± SEM = 0.39 ± 0.01 μM) was found to be the most potent inhibitor of h-NPP1 and compound 5h (IC50 ± SEM = 1.02 ± 0.05 μM) was found to be the most potent inhibitor of h-NPP3. Similarly, for fluorinated thiadiazolopyrimidones, derivative 6e (IC50 ± SEM = 0.31 ± 0.01 μM) exhibited the best inhibition of NPP1 and it was found that this compound exhibited ≈28 fold improvement in inhibitory potential as compared with the reference control i.e. Suramin (IC50 ± SEM = 8.67 ± 1.3 μM). Moreover, homology modelling and molecular docking studies of both inhibitors were carried out to suggest the putative binding mode of inhibitors with the respective enzyme i.e. h-NPP1 and h-NPP3.

A range of 3-alkynylated 3-deoxy-estrones were prepared by Sonogashira reactions and transformed into estrone derived diones and quinoxalines. The alkynylated estrones and their derivatives exhibit significant biological activity as alkaline phosphatase inhibitors. The mode of action was illustrated based on docking studies.

Palladium-catalyzed cross-couplings of O-peracylated and O-permethylated 2,6-anhydro-aldose tosylhydrazones with aryl halides were studied under thermic conditions in the presence of LiOtBu and phosphine ligands. The reactions gave the corresponding aryl substituted exo-glycals as mixtures of diastereomers in 11–75% yields. The transformations represent a new access to these types of glycomimetic compounds. The double bond of some aryl substituted exo-glycals was saturated to give good yields of benzylic C-glycosyl derivatives.

A new and convenient synthesis of optically pure (S)-2-amino-5-[aryl]pent-4-ynoic acids (alkynylated amino acids) is reported. (S)-2-Aminopent-4-ynoic acid-Ni-(S)-BPB was prepared and then functionalized via Sonogashira cross-coupling reactions to give (S)-2-amino-5-[aryl]pent-4-ynoic acid-Ni-(S)-BPB. The reaction conditions for the cross-coupling reaction were optimized and twelve derivatives were synthesized. Afterwards the Ni-complexes were cleaved to obtain the free (S)-2-amino-5-[aryl]pent-4-ynoic acids with excellent optical purity. The prepared (S)-2-amino-5-[aryl]pent-4-ynoic acids were tested for biological activity and selectively showed high inhibitory activity against aldose reductase (ALR2) over ALR1. Molecular docking studies have also been carried out to identify the putative binding mode of the compounds in these enzymes.

A variety of mono- and diethynyl substituted fluorinated benzene derivatives was prepared by Sonogashira cross coupling reactions of 1,2-dibromo-3,5-difluorobenzene. The reactions proceed with very good site-selectivity in favor of position 1, due to electronic and steric reasons.

A particle is projected from a point P in a subset E of a convex region H to a point Q in a uniformly random direction. The probability that Q lies in the interior of H at time t is obtained for two types of motion of the particle, rectilinear (i.e. straight-line) and Brownian. In the case of rectilinear motion, the first passage time through the boundary of H is considered. Results are obtained in terms of the generalized overlap function for embedded bodies.

Objective To quantify changes in the chondrocyte metabolism of aggrecan core protein and type II procollagen messenger RNA (mRNA) during the early and middle phases of experimental osteoarthritis (OA) in animals. Methods Experimental OA was induced by transecting the cranial cruciate ligament of the stifle joint in adult animals; articular cartilage was harvested and analyzed after 4, 10, and 32 weeks. Results Northern blot analysis revealed no change in aggrecan mRNA 4 weeks after surgery compared with aggrecan mRNA in the unoperated contralateral control joints; aggrecan mRNA levels became significantly elevated by 10 and 32 weeks after surgery. In OA cartilage, type II procollagen mRNA was dramatically and progressively elevated at all times after surgery. The relative increases in type II procollagen mRNA exceeded the relative increases in aggrecan mRNA at all times after surgery, and these differences increased progressively over time. Articular chondrocytes became activated globally (total RNA increases) and specifically (mRNA increase) early after joint injury and remained activated throughout the early and middle phases of this experimental OA. Conclusion The early natural history of experimental OA is characterized by a progressive imbalance in the mRNA expression of aggrecan and type II procollagen in articular chondrocytes. These results suggest that the stimuli for the transcription of these 2 genes are fundamentally different in this animal model.