Copenhagen Diabetes Consensus (CODIAC) 2021: User involvement in diabetes care, prevention and research.

AIMS: User involvement is pivotal for health development, but there are significant gaps in our understanding of the concept. The Copenhagen Diabetes Consensus on User Involvement in Diabetes Care, Prevention and Research (CODIAC) was established to address these gaps, share knowledge and develop best practices. METHODS: A literature review of user involvement was undertaken in diabetes care, prevention and research. Moreover, a Group Concept Mapping (GCM) survey synthesized the knowledge and opinions of researchers, healthcare professionals and people with diabetes and their carers to identify gaps between what is important for user involvement and what is being done in practice. Finally, a consensus conference discussed the main gaps in knowledge and practice while developing plans to address the shortcomings. RESULTS: The literature review demonstrated that user involvement is an effective strategy for diabetes care, prevention and research, given the right support and conditions, but gaps and key challenges regarding the value and impact of user involvement approaches were found. The GCM process identified 11 major gaps, where important issues were not being sufficiently practised. The conference considered these gaps and opportunities to develop new collaborative initiatives under eight overall themes. CONCLUSIONS: User involvement is effective and adds value to diabetes care, prevention and research when used under the right circumstances. CODIAC developed new learning about the way in which academic and research knowledge can be transferred to more practice-oriented knowledge and concrete collaborative initiatives. This approach may be a potential new framework for initiatives in which coherence of process can lead to coherent outputs.

Structural remodelling of the carbon-phosphorus lyase machinery by a dual ABC ATPase.

In Escherichia coli, the 14-cistron phn operon encoding carbon-phosphorus lyase allows for utilisation of phosphorus from a wide range of stable phosphonate compounds containing a C-P bond. As part of a complex, multi-step pathway, the PhnJ subunit was shown to cleave the C-P bond via a radical mechanism, however, the details of the reaction could not immediately be reconciled with the crystal structure of a 220 kDa PhnGHIJ C-P lyase core complex, leaving a significant gap in our understanding of phosphonate breakdown in bacteria. Here, we show using single-particle cryogenic electron microscopy that PhnJ mediates binding of a double dimer of the ATP-binding cassette proteins, PhnK and PhnL, to the core complex. ATP hydrolysis induces drastic structural remodelling leading to opening of the core complex and reconfiguration of a metal-binding and putative active site located at the interface between the PhnI and PhnJ subunits.

A Community-Based, Participatory, Multi-Component Intervention Increased Sales of Healthy Foods in Local Supermarkets-The Health and Local Community Project (SoL).

Project SoL was a 19-month (September 2012 to April 2014) community-based multi-component intervention based on the supersetting approach that was designed to promote healthier eating and physical activity among children and their families. The aim of this study was to examine the effects of a multi-component intervention (level 1) and a mass media intervention alone (level 2) compared to a control area (level 3) on food sales. The design was quasi-experimental. Weekly sales data for all Coop supermarkets in the intervention and control areas were analysed via longitudinal linear mixed-effects analyses. Significant increases in the sales of fish (total) (29%; p = 0.003), canned fish (31%; p = 0.025) and oatmeal (31%; p = 0.003) were found for the level 1 intervention area compared to the control area. In the level 2 intervention area, significant increases in the sales of vegetables (total) (17%; p = 0.038), fresh vegetables (20%; p = 0.01), dried fruit (51%; p = 0.022), oatmeal (19%; p = 0.008) and wholegrain pasta (58%; p = 0.0007) were found compared to the control area. The sales of canned fish increased by 30% in the level 1 area compared to the level 2 area (p = 0.025). This study demonstrated significant increases in the sales of healthy foods, both in the areas with multi-component and mass media interventions alone compared to the control area.

A mobile observatory powered by sun and wind for near real time measurements of atmospheric, glacial, terrestrial, limnic and coastal oceanic conditions in remote off-grid areas.

Climate change is rapidly altering the Arctic environment. Although long-term environmental observations have been made at a few locations in the Arctic, the incomplete coverage from ground stations is a main limitation to observations in these remote areas. Here we present a wind and sun powered multi-purpose mobile observatory (ARC-MO) that enables near real time measurements of air, ice, land, rivers, and marine parameters in remote off-grid areas. Two test units were constructed and placed in Northeast Greenland where they have collected data from cabled and wireless instruments deployed in the environment since late summer 2021. The two units can communicate locally via WiFi (units placed 25 km apart) and transmit near-real time data globally over satellite. Data are streamed live and accessible from (https://gios.org). The cost of one mobile observatory unit is c. 304.000€. These test units demonstrate the possibility for integrative and automated environmental data collection in remote coastal areas and could serve as models for a proposed global observatory system.

Impact of school-based nutrition and physical activity intervention on body mass index eight years after cessation of randomized controlled trial (AVall study).

BACKGROUND & AIMS: The prevalence of obesity and overweight among children is increasing, representing a new and pressing societal problem. Excess weight in childhood is an independent risk factor for adult obesity. Although school-based interventions are generally considered effective in the short term, few studies analyze their longterm impact. The aim of study was to assess if the effect of the intervention on body mass Index (BMI) immediately after the intervention remained eight years later (AVall Study). METHODS: In 2006-2008, an intervention for primary school children promoted healthy eating habits and physical activity in the school setting using the Investigation, Vision, Action and Change (IVAC) educational methodology, which involves children as active participants in healthy change. At baseline, parents reported their weight, height and educational level by questionnaire. Children's weight and height were measured in situ in 2006, 2008, 2010, 2012 and 2016, and levels of physical activity were assessed by questionnaire. Multilevel mixed effects linear regression was used to assess changes in BMI over time. RESULTS: Increases in BMI from 2006 to 2016 were 0.68 kg/m2 (95% CI, 0.02, 1.34; P = 0.045) higher in the control group than in the intervention group. The prevalence of obesity and overweight combined in 2006 and 2016 was 22.2% and 27.9%, respectively, in the control group and 25.6% and 21.2% respectively, in the intervention group. Changes in BMI in the intervention group were maintained from 2006 on: at the end of the intervention in 2008, -0.4 kg/m2 (P = 0.001); in 2010, -0.23 g/m2 (P = 0.012); in 2012, -0.63 kg/m2 (P < 0.001) and in 2016, -0.27 kg/m2 (P = 0.025). The child's BMI increased by 0.52 kg/m2 (P = 0.046) if the father was obese, by 1.26 kg/m2 (p = 0.011) if the mother was obese, and by 2.37 kg/m2 (P < 0.001) if both parents were obese. Parental education levels were not associated with childhood obesity. CONCLUSIONS: A school-based healthy eating habits and physical activity intervention using IVAC methodology contributed to lower increases in BMI among children in primary school. Although parental BMI also influenced children's BMI, the intervention was effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT01156805.

The Prodigal Compound: Return of Ribosyl 1,5-Bisphosphate as an Important Player in Metabolism.

Ribosyl 1,5-bisphosphate (PRibP) was discovered 65 years ago and was believed to be an important intermediate in ribonucleotide metabolism, a role immediately taken over by its "big brother" phosphoribosyldiphosphate. Only recently has PRibP come back into focus as an important player in the metabolism of ribonucleotides with the discovery of the pentose bisphosphate pathway that comprises, among others, the intermediates PRibP and ribulose 1,5-bisphosphate (cf. ribose 5-phosphate and ribulose 5-phosphate of the pentose phosphate pathway). Enzymes of several pathways produce and utilize PRibP not only in ribonucleotide metabolism but also in the catabolism of phosphonates, i.e., compounds containing a carbon-phosphorus bond. Pathways for PRibP metabolism are found in all three domains of life, most prominently among organisms of the archaeal domain, where they have been identified either experimentally or by bioinformatic analysis within all of the four main taxonomic groups, Euryarchaeota, TACK, DPANN, and Asgard. Advances in molecular genetics of archaea have greatly improved the understanding of the physiology of PRibP metabolism, and reconciliation of molecular enzymology and three-dimensional structure analysis of enzymes producing or utilizing PRibP emphasize the versatility of the compound. Finally, PRibP is also an effector of several metabolic activities in many organisms, including higher organisms such as mammals. In the present review, we describe all aspects of PRibP metabolism, with emphasis on the biochemical, genetic, and physiological aspects of the enzymes that produce or utilize PRibP. The inclusion of high-resolution structures of relevant enzymes that bind PRibP provides evidence for the flexibility and importance of the compound in metabolism.

The Abc of Phosphonate Breakdown: A Mechanism for Bacterial Survival.

Bacteria have evolved advanced strategies for surviving during nutritional stress, including expression of specialized enzyme systems that allow them to grow on unusual nutrient sources. Inorganic phosphate (Pi ) is limiting in most ecosystems, hence organisms have developed a sophisticated, enzymatic machinery known as carbon-phosphorus (C-P) lyase, allowing them to extract phosphate from a wide range of phosphonate compounds. These are characterized by a stable covalent bond between carbon and phosphorus making them very hard to break down. Despite the challenges involved in both synthesizing and catabolizing phosphonates, they are widespread in nature. The enzymes required for the bacterial C-P lyase pathway have been identified and for the most part structurally characterized. Nevertheless, the mechanistic principles governing breakdown of phosphonate compounds remain enigmatic. In this review, an overview of the C-P lyase pathway is provided and structural aspects of the involved enzyme complexes are discussed with a special emphasis on the role of ATP-binding cassette (ABC) proteins.

Project SoL-A Community-Based, Multi-Component Health Promotion Intervention to Improve Healthy Eating and Physical Activity Practices among Danish Families with Young Children Part 2: Evaluation.

Project SoL is implemented over a period of four years with the aim to promote healthy eating and physical activity among children aged 3⁻8 years by targeting the families in a Danish municipality based on the multi-component, supersetting strategy. Interventions are implemented in childcare centres, schools and supermarkets in three local communities as well as in local mass media and social media during a 19 months period in the Municipality of Bornholm. The matching Municipality of Odsherred serves as a control site based on its similarity to Bornholm regarding several socio-demographic and health indicators. The present paper gives an account of the design used for the summative and formative evaluation based on a realistic evaluation and a mixed methods approach combining qualitative and quantitative methods. Summative studies are conducted on changes of health behaviours among the involved families and within the municipalities in general, changes in community awareness of the project, changes in purchase patterns, changes in overweight and obesity among the targeted children and changes in knowledge and preferences among children due to sensory education workshops. The formative research comprises studies on children's perceptions of health, perceptions of staff at supermarkets and media professionals on their roles in supporting the health promotion agenda, and motivations and barriers of community stakeholders to engage in health promotion at community level. The paper discusses operational issues and lessons learnt related to studying complex community interventions, cross-disciplinarily, interfaces between practice and research and research capacity strengthening; and suggests areas for future research. The development and implementation of the intervention and its theoretical foundation is described in a separate paper.

Methylphosphonic Acid Biosynthesis and Catabolism in Pelagic Archaea and Bacteria.

Inorganic phosphate is essential for all life forms, yet microbes in marine environments are in near constant deprivation of this important nutrient. Organophosphonic acids can serve as an alternative source of inorganic phosphate if microbes possess the appropriate biochemical pathways that allow cleavage of the stable carbon-phosphorus bond that defines this class of molecule. One prominent source of inorganic phosphate is methylphosphonic acid, which is found as a constituent of marine-dissolved organic matter. The cycle of biosynthesis and catabolism of methylphosphonic acid by marine microbes is the likely source of supersaturating levels of methane in shallow ocean waters. This review provides an overview of the rich biochemistry that has evolved to synthesize methylphosphonic acid and catabolize this molecule into Pi and methane, with an emphasis on the reactions catalyzed by methylphosphonic acid synthase MpnS and the carbon-phosphorus lyase system. The protocols and experiments that are described for MpnS and carbon-phosphorus lyase provide a foundation for studying the structures and mechanisms of these and related enzymes.

Project SoL-A Community-Based, Multi-Component Health Promotion Intervention to Improve Eating Habits and Physical Activity among Danish Families with Young Children. Part 1: Intervention Development and Implementation.

Project SoL was implemented over a period of four years from 2012⁻2015 with the aim to promote healthy eating and physical activity among families with children aged 3⁻8 years, living in selected communities in two Danish municipalities. This was done by applying the supersetting approach to implement complex multi-component interventions in a participatory, coordinated, and integrated manner in childcare centres, schools, and supermarkets in three local communities, as well as in local media during a 19-month period in the Regional Municipality of Bornholm, which served as the intervention site. The matching municipality of Odsherred served as a control site based on its similarity to Bornholm regarding several socio-demographic and health indicators. The present paper describes the design of Project SoL as well as the processes of developing and implementing its complex interventions. Moreover, the theoretical and conceptual framework of the project is described together with its organisational structure, concrete activities, and sustainability measures. The paper discusses some of the key lessons learned related to participatory development and the implementation of a multi-component intervention. The paper concludes that coordinated and integrated health promotion activities that are implemented together with multiple stakeholders and across multiple settings in the local community are much more powerful than individual activities carried out in single settings. The supersetting approach was a useful conceptual framework for developing and implementing a complex multi-component health promotion intervention and for fostering ownership and sustainability of the intervention in the local community. The research and evaluation approach of the project is described in a separate paper (Part 2).

Spring Melt and the Redistribution of Organochlorine Pesticides in the Sea-Ice Environment: A Comparative Study between Arctic and Antarctic Regions.

Complementary sampling of air, snow, sea-ice, and seawater for a range of organochlorine pesticides (OCPs) was undertaken through the early stages of respective spring sea-ice melting at coastal sites in northeast Greenland and eastern Antarctica to investigate OCP concentrations and redistribution during this time. Mean concentrations in seawater, sea-ice and snow were generally greater at the Arctic site. For example, α-HCH was found to have the largest concentrations of all analytes in Arctic seawater and sea-ice meltwater samples (224-253 and 34.7-48.2 pg·L-1 respectively compared to 1.0-1.3 and <0.63 pg·L-1 respectively for Antarctic samples). Differences in atmospheric samples were generally not as pronounced however. Findings suggest that sea-ice OCP burdens originate from both snow and seawater. The distribution profile between seawater and sea-ice showed a compound-dependency for Arctic samples not evident with those from the Antarctic, possibly due to full submersion of sea-ice at the former. Seasonal sea-ice melt processes may alter the exchange rates of selected OCPs between air and seawater, but are not expected to reverse their direction, which fugacity modeling indicates is volatilisation in the Arctic and net deposition in the Antarctic. These predictions are consistent with the limited current observations.

Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance.

Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.

The involvement of young people in school- and community-based noncommunicable disease prevention interventions: a scoping review of designs and outcomes.

BACKGROUND: Since stakeholders' active engagement is essential for public health strategies to be effective, this review is focused on intervention designs and outcomes of school- and community-based noncommunicable disease (NCD) prevention interventions involving children and young people. METHODS: The review process was based on the principles of scoping reviews. A systematic search was conducted in eight major databases in October 2015. Empirical studies published in English, French, Portuguese, and Spanish were considered. Five selection criteria were applied. Included in the review were (1) empirical studies describing (2) a health intervention focused on diet and/or physical activity, (3) based on children's and young people's involvement that included (4) a relationship between school and local community while (5) providing explicit information about the outcomes of the intervention. The search provided 3995 hits, of which 3253 were screened by title and abstract, leading to the full-text screening of 24 papers. Ultimately, 12 papers were included in the review. The included papers were analysed independently by at least two reviewers. RESULTS: Few relevant papers were identified because interventions are often either based on children's involvement or are multi-setting, but rarely both. Children were involved through participation in needs assessments, health committees and advocacy. School-community collaboration ranged from shared activities, to joint interventions with common goals and activities. Most often, collaboration was school-initiated. Most papers provided a limited description of the outcomes. Positive effects were identified at the organisational level (policy, action plans, and healthy environments), in adult stakeholders (empowerment, healthy eating) and in children (knowledge, social norms, critical thinking, and health behaviour). Limitations related to the search and analytical methods are discussed. CONCLUSION: There are very few published studies on the effectiveness of interventions based on children's involvement in school- and community-based NCD prevention programmes. However, interventions with these characteristics show potential benefits, and the merits of complex multi-setting approaches should be further explored through intervention-based studies assessing their effectiveness and identifying which components contribute to the observed outcomes.

Structural insights into the bacterial carbon-phosphorus lyase machinery.

Phosphorus is required for all life and microorganisms can extract it from their environment through several metabolic pathways. When phosphate is in limited supply, some bacteria are able to use phosphonate compounds, which require specialized enzymatic machinery to break the stable carbon-phosphorus (C-P) bond. Despite its importance, the details of how this machinery catabolizes phosphonates remain unknown. Here we determine the crystal structure of the 240-kilodalton Escherichia coli C-P lyase core complex (PhnG-PhnH-PhnI-PhnJ; PhnGHIJ), and show that it is a two-fold symmetric hetero-octamer comprising an intertwined network of subunits with unexpected self-homologies. It contains two potential active sites that probably couple phosphonate compounds to ATP and subsequently hydrolyse the C-P bond. We map the binding site of PhnK on the complex using electron microscopy, and show that it binds to a conserved insertion domain of PhnJ. Our results provide a structural basis for understanding microbial phosphonate breakdown.

Evaluation of an ICD-10 algorithm to detect osteonecrosis of the jaw among cancer patients in the Danish National Registry of Patients.

PURPOSE: This study aimed to validate a predefined algorithm for osteonecrosis of the jaw (ONJ) among cancer patients in the Danish National Registry of Patients and to assess the nature of clinical information recorded in medical charts of ONJ patients. METHODS: We identified potential ONJ cases recorded in 2005-2010 among cancer patients at the hospital Departments of Oral and Maxillofacial Surgery (DOMS) in three Danish regions, using a set of codes from the International Classification of Diseases, 10th revision (ICD-10). We abstracted DOMS charts of the potential cases, had the ONJ status adjudicated by an expert ONJ adjudication committee (ONJAC), and computed positive predictive values. For patients with ONJAC-confirmed ONJ, we abstracted the charts for information on ONJ clinical course. Sensitivity of the algorithm was computed using a separate sample of 101 known ONJ cases accrued in 2005-2011. RESULTS: We identified 212 potential ONJ cases, of which 197 (93%) had charts available for abstraction. Eighty-three potential cases were confirmed by ONJAC, with a positive predictive value of 42% (95% confidence interval [CI] 35%-49%). DOMS charts of these 83 cases contained complete information on ONJ clinical course. Information about antiresorptive treatment was recorded for 84% of the patients. Among the 101 known ONJ cases, 74 had at least one prespecified ICD-10 code recorded in the Danish National Registry of Patients within ±90 days of the ONJ diagnosis (sensitivity 73%; 95%CI [64%-81%]). CONCLUSIONS: The predefined algorithm is not adequate for monitoring ONJ in pharmacovigilance studies. Additional case-finding approaches, coupled with adjudication, are necessary to estimate ONJ incidence accurately.

Designing for health in school buildings: between research and practice.

AIM: To investigate the kinds of knowledge practitioners use when planning and designing for health in school buildings. METHODS: Twelve semi-structured qualitative interviews were conducted with architects, teachers and officials to investigate use of knowledge in the making of school buildings. RESULTS: Practitioners drew on many kinds and sources of knowledge, but in particular they made use of concepts, examples or pictures or thought-provoking knowledge. However, the interviews indicate a number of hurdles for efficient knowledge sharing between research and practice: (1) a considerable discrepancy between kinds of knowledge used by practice and knowledge traditionally produced by research; (2) research-knowledge and practice-knowledge form two circuits and the flow from one circuit to the other is weak; (3) practitioners' knowledge was often based on experience and therefore person-dependent. It makes the knowledge vulnerable. CONCLUSIONS: Special attention has to be paid by research to concepts and principles to guide the decision-making in practice. Further is recommended to consider new kinds of collaboration between researchers and practitioners.

Structure of dimeric, recombinant Sulfolobus solfataricus phosphoribosyl diphosphate synthase: a bent dimer defining the adenine specificity of the substrate ATP.

The enzyme 5-phosphoribosyl-1-α-diphosphate (PRPP) synthase (EC 2.7.6.1) catalyses the Mg(2+)-dependent transfer of a diphosphoryl group from ATP to the C1 hydroxyl group of ribose 5-phosphate resulting in the production of PRPP and AMP. A nucleotide sequence specifying Sulfolobus solfataricus PRPP synthase was synthesised in vitro with optimised codon usage for expression in Escherichia coli. Following expression of the gene in E. coli PRPP synthase was purified by heat treatment and ammonium sulphate precipitation and the structure of S. solfataricus PRPP synthase was determined at 2.8 Å resolution. A bent dimer oligomerisation was revealed, which seems to be an abundant feature among PRPP synthases for defining the adenine specificity of the substrate ATP. Molecular replacement was used to determine the S. solfataricus PRPP synthase structure with a monomer subunit of Methanocaldococcus jannaschii PRPP synthase as a search model. The two amino acid sequences share 35 % identity. The resulting asymmetric unit consists of three separated dimers. The protein was co-crystallised in the presence of AMP and ribose 5-phosphate, but in the electron density map of the active site only AMP and a sulphate ion were observed. Sulphate ion, reminiscent of the ammonium sulphate precipitation step of the purification, seems to bind tightly and, therefore, presumably occupies and blocks the ribose 5-phosphate binding site. The activity of S. solfataricus PRPP synthase is independent of phosphate ion.

Stability of the anterior maxillary segment and teeth after segmental le fort I osteotomy and postoperative skeletal elastic fixation with or without occlusal splint.

OBJECTIVES: To assess the short term dental and skeletal stability of the anterior maxillary segment after segmental Le Fort I osteotomy with postoperative skeletal elastic fixation with or without occlusal splint. MATERIAL AND METHODS: 29 consecutive patients underwent segmental Le Fort I osteotomy and elastic skeletal fixation was applied. Patients were divided into two groups according to whether a fixed occlusal splint was used for six weeks (group A) or dismounted perioperatively (group B). Changes in landmarks and reference planes between the two timepoints were estimated on lateral cephalometric radiographs. GROUP A: The upper incisor had a mean intrusion of -0.56 mm (SD 0.77; range -2.04 to 1.08 mm) and a mean posterior movement of -0.93 mm (SD 1.03; range -2.52 to 0.96 mm). The mean change in the axial inclination of the upper incisor was -0.33° (SD 2.56; range -6° to 4°) (95% CI: -1.75 to 1.08°). Group B: The upper incisor had a mean intrusion of -0.13 mm (SD 1.36; range -1.92 to 3.6 mm) and a mean anterior movement of 0.11 mm (SD 1.78; range -2.88 to 3.84 mm). The mean change in the axial inclination of the upper incisor was -0.07° (SD 3.05; range -5° to 5°) (95% CI: -1.83 to 1.69°). There was no statistically significant difference in stability between the two groups at the P value 0.05. CONCLUSIONS: The skeletal anterior fixation with postoperative elastics for eight weeks may not compromise the early postoperative dental and skeletal stability of the anterior segment in segmental Le Fort I osteotomy.