Local inhibition of indoleamine 2, 3-dioxygenase mitigates renal fibrosis

Chronic kidney disease (CKD) is a major global health concern and renal fibrosis is an integral part of the pathophysiological mechanism underlying disease progression. In CKD patients, the majority of metabolic pathways are in disarray and perturbations in enzyme activity most likely contribute to the wide variety of comorbidities observed in these patients. To illustrate, catabolism of tryptophan by indoleamine 2,3-dioxygenase (IDO) gives rise to numerous biologically active metabolites implicated in CKD progression. Here, we evaluated the effect of antagonizing IDO on renal fibrogenesis. To this end, we antagonized IDO using 1-methyl-D-tryptophan (1-MT) and BMS-98620 in TGF-β-treated murine precision-cut kidney slices (mPCKS) and in mice subjected to unilateral ureteral obstruction (UUO). The fibrotic response was evaluated on both the gene and protein level using qPCR and western blotting. Our results demonstrated that treatment with 1-MT or BMS-985205 markedly reduced TGF-β-mediated fibrosis in mPCKS, as seen by a decreased expression of collagen type 1, fibronectin, and α-smooth muscle actin. Moreover, IDO protein expression clearly increased following UUO, however, treatment of UUO mice with either 1-MT or BMS-986205 did not significantly affect the gene and protein expression of the tested fibrosis markers. However, both inhibitors significantly reduced the renal deposition of collagen in UUO mice as shown by Sirius red and trichrome staining. In conclusion, this study demonstrates that IDO antagonism effectively mitigates fibrogenesis in mPCKS and reduces renal collagen accumulation in UUO mice. These findings warrant further research into the clinical application of IDO inhibitors for the treatment of renal fibrosis

Speaking Up for Fundamental Care: the ILC Aalborg Statement.

OBJECTIVE: The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems. KEY ARGUMENTS: We present five propositions for radically transforming fundamental care delivery:Value: fundamental care must be foundational to all caring activities, systems and institutionsTalk: fundamental care must be explicitly articulated in all caring activities, systems and institutions.Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions.Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care. RESEARCH: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula. CONCLUSION: For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team-educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians-value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change

Acceptance and expectance: Cultural norms for alcohol use in Denmark

Alcohol consumption levels in Denmark are high with the risk of increased morbidity and mortality in the population. It is suggested that people's views of “normal” use of alcohol must be the platform for formulating effective alcohol education and prevention strategies. However, little is known about the cultural norms for alcohol use. The aim of this article is to examine the perceptions of cultural norms for alcohol use in Denmark among different age groups and the similarities and differences between the groups, including examining how people construct and negotiate the cultural norms for drinking. Five focus group interviews were conducted with one group per the following age groups: 16–20; 21–34; 35–44; 45–64; and 65–82. These groups consisted of both men and women with five to six participants in each group (a total of 27). Thematic analysis was performed with the aim of developing themes that reflected the cultural norms for alcohol use. The unifying theme of this research was Danish people's acceptance and expectance of social drinking. Alcohol is widely accepted and associated with mutual expectations to drink, leading to identification of cultural influences and facilitation to drink. The social drinking context plays an important role in people's perceptions of the normality of drinking. This includes the selection of particular beverages, and regularly leads to consumption above the recommended levels for low risk to health. This calls for public health attention that promotes low risk drinking in the social context and aims to prevent and reduce serious alcohol-related harm and health problems across the population

The DanTIN project – creating a platform for describing the grammar of Danish talk-in-interaction

The article introduces a new website, samtalegrammatik.dk ('grammar of talk-in-interaction'), it describes the methods used for constructing the website, and it provides descriptions of three new grammatical phenomena in Danish talk-in-interaction. The website is a result of investigations carried out by the research group DanTIN ('Danish talk-in-interaction') since 2009. Until 2013, the group has published analyses of quite diverse phenomena, such as different versions of the word hvad 'what' that seem to belong to different word classes and have different functions in talk-ininteraction, the distribution of the hesitation marker øh(m) 'uh(m)', or different word orders after the conjunction fordi ('because'). These phenomena were selected because they were clearly different from written Danish. By launching the website samtalegrammatik.dk the group takes a step towards building a comprehensive grammar of Danish talk-in-interaction. It offers a template for a description of all aspects of the grammar of Danish talk-in-interaction, even though at the time of the launching only a little part of the entries will be filled in. The idea is that the investigations will be continued in many years to come, and, thus, the website will grow and become more complete. The three phenomena reported in some detail here all have intonation as an important part of their grammatical descriptions. They are (1) the particle nå (roughly 'oh'), (2) exaggerated pitch as a story ending device, and (3) the interjection ej, which is an intranslatable exclamation word. FGW – Publications without University Leiden contrac

Speaking up for Fundamental Care: The ILC Aalborg Statement

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems. Key arguments We present five propositions for radically transforming fundamental care delivery: Value: fundamental care must be foundational to all caring activities, systems and institutions Talk: fundamental care must be explicitly articulated in all caring activities, systems and institutions. Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions. Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care. Research: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula. Conclusion For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team - educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians - value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change

Fundamental questions and applications of sclerochronology: Community-defined research priorities.

Horizon scanning is an increasingly common strategy to identify key research needs and frame future agendas in science. Here, we present the results of the first such exercise for the field of sclerochronology, thereby providing an overview of persistent and emergent research questions that should be addressed by future studies. Through online correspondence following the 5th International Sclerochronology Conference in 2019, participants submitted and rated questions that addressed either knowledge gaps or promising applications of sclerochronology. An initial list of 130 questions was compiled based on contributions of conference attendees and reviewed by expert panels formed during the conference. Herein, we present and discuss the 50 questions rated to be of the highest priority, determined through an online survey distributed to sclerochronology community members post the conference. The final list (1) includes important questions related to mechanisms of biological control over biomineralization, (2) highlights state of the art applications of sclerochronological methods and data for solving long-standing questions in other fields such as climate science and ecology, and (3) emphasizesthe need for common standards for data management and analysis. Although research priorities are continually reassessed, our list provides a roadmap that can be used to motivate research efforts and advance sclerochronology towardnew, and more powerful, applications.N/

Fundamental questions and applications of sclerochronology: Community-defined research priorities

Horizon scanning is an increasingly common strategy to identify key research needs and frame future agendas in science. Here, we present the results of the first such exercise for the field of sclerochronology, thereby providing an overview of persistent and emergent research questions that should be addressed by future studies. Through online correspondence following the 5th International Sclerochronology Conference in 2019, participants submitted and rated questions that addressed either knowledge gaps or promising applications of sclerochronology. An initial list of 130 questions was compiled based on contributions of conference attendees and reviewed by expert panels formed during the conference. Herein, we present and discuss the 50 questions rated to be of the highest priority, determined through an online survey distributed to sclerochronology community members post the conference. The final list: (1) includes important questions related to mechanisms of biological control over biomineralization; (2) highlights state of the art applications of sclerochronological methods and data for solving long-standing questions in other fields such as climate science and ecology: and (3) emphasizes the need for common standards for data management and analysis. Although research priorities are continually reassessed, our list provides a roadmap that can be used to motivate research efforts and advance sclerochronology toward new, and more powerful, applications