Supporting the Community to Embrace Individuals with Dementia and to Be More Inclusive: Findings of a Conceptual Framework Development Study.

The number of community-dwelling people with dementia (PwD) is rising, and the role of their relatives is crucial in addressing and mitigating the implications of dementia on health care systems and on society. We developed a new conceptual framework to promote the collaboration of the community in supporting relatives who are caring for a PwD as well as a range of stakeholders in embracing dementia. A qualitatively driven, multi-method study divided into three phases was performed from 2019 to 2021. A qualitative descriptive study, a mixed-method systematic review and three consensus workshops were conducted, and their results were triangulated. The final version of the Community Collaboration Concept Framework is composed of three main domains based upon seven components: (1) embracing dementia; (2) creating empowerment and a sense of community; (3) collaborating through cocreation and design thinking. The new framework is based on the literature, the synthesis of empirical data and the consensus of a panel of international experts, supporting the global goal of improving community inclusiveness and collaboration. Further studies are needed to confirm its validity, how it should be implemented in practice in various settings and to propose improvements when designing projects based upon it.

Needs, issues, and expectations on dementia care at home across Europe to inform policy development: Findings from a transnational research study.

This qualitative descriptive study explored needs, issues, and expectations on dementia care at home as expressed by relatives of people living with dementia (PwD), health and social care professionals (HSCPs), and members of civil society organisations (CSOs) from four European countries. A focus group methodology integrated with individual semi-structured interviews was adopted to collect data by employing a purposeful sampling method. A total of 13 focus groups and 12 individual interviews were conducted in 2019, involving 65 relatives of PwD, 32 HSCPs, and 23 members of CSOs. Deductive content analysis and findings triangulation were performed to analyse data, and a subgroup of participants confirmed the findings. Relatives need to be (a) informed and trained to cope with changes in PwD, (b) recognised for their caregiving role, and (c) assisted by specialised HSCPs. Professionals who work in partnership with PwD and their relatives call for a reorganisation of available services. CSOs compensate for the lack of proper support, promoting networks, and cooperation with local communities. Several commonalities emerged across countries, highlighting the chance to inform and develop common policies to improve the quality of life of PwD and their relatives across Europe. Policies improving person- and family-centred care and spreading dementia-friendly community concepts and practices are suggested. Strong collaborations between formal and informal services and communities are also needed as well as information on educational strategies to improve the use of resources, promote PwD care, and support PwD relatives' needs.

Structure and dynamics of highly concentrated LiTFSI/acetonitrile electrolytes.

High salt concentration has been shown to induce increased electrochemical stability in organic solvent-based electrolytes. Accompanying the change in bulk properties is a structural ordering on mesoscopic length scales and changes in the ion transport mechanism have also been suggested. Here we investigate the local structure and dynamics in highly concentrated acetonitrile electrolytes as a function of salt concentration. Already at low concentrations ordering on microscopic length scales in the electrolytes is revealed by small angle X-ray scattering, as a result of correlations of Li+ coordinating clusters. For higher salt concentrations a charge alternation-like ordering is found as anions start to take part in the solvation. Results from quasi-elastic neutron spectroscopy reveal a jump diffusion dynamical process with jump lengths virtually independent of both temperature and Li-salt concentration. The jump can be envisaged as dissociation of a solvent molecule or anion from a particular Li+ solvation structure. The residence time, 50-800 ps, between the jumps is found to be highly temperature and Li-salt concentration dependent, with shorter residence times for higher temperature and lower concentrations. The increased residence time at high Li-salt concentration can be attributed to changes in the interaction of the solvation shell as a larger fraction of TFSI anions take part in the solvation, forming more stable solvation shells.

Pressure and Temperature Dependence of Local Structure and Dynamics in an Ionic Liquid.

A detailed understanding of the local dynamics in ionic liquids remains an important aspect in the design of new ionic liquids as advanced functional fluids. Here, we use small-angle X-ray scattering and quasi-elastic neutron spectroscopy to investigate the local structure and dynamics in a model ionic liquid as a function of temperature and pressure, with a particular focus on state points (P,T) where the macroscopic dynamics, i.e., conductivity, is the same. Our results suggest that the initial step of ion transport is a confined diffusion process, on the nanosecond timescale, where the motion is restricted by a cage of nearest neighbors. This process is invariant considering timescale, geometry, and the participation ratio, at state points of constant conductivity, i.e., state points of isoconductivity. The connection to the nearest-neighbor structure is underlined by the invariance of the peak in the structure factor corresponding to nearest-neighbor correlations. At shorter timescales, picoseconds, two localized relaxation processes of the cation can be observed, which are not directly linked to ion transport. However, these processes also show invariance at isoconductivity. This points to that the overall energy landscape in ionic liquids responds in the same way to density changes and is mainly governed by the nearest-neighbor interactions.

Access and Use of Device-Aided Therapies for Parkinson's Disease in Denmark.

BACKGROUND: In Denmark's five regions, there is potential inequality in access to device-aided therapy (DAT) for Parkinson's disease (PD) based on structural or socioeconomic factors. It is unclear how long DAT is maintained and affects concomitant medication. OBJECTIVES: To investigate access to DAT by comparing the proportion of patients with DBS, subcutaneous apomorphine infusion (SCAI), or levodopa/carbidopa intestinal gel (LCIG) in Danish regions 2008-2016 and describe demographics of patients, changes in use of comedication, and maintenance of DAT. METHODS: This work is a retrospective nationwide population-based registry analysis generated by combining various registries and statistics in Denmark. RESULTS: From 2008 to 2016, 612 patients started DAT. There were statistically significant differences in the number of patients starting DAT between the Capital Region (99.5 per 1,000) and both Central Jutland (66.6 per 1,000) and North Jutland (70.6 per 1,000; P < 0.05). Among DBS and LCIG patients, respectively, 4% and 42% were aged ≥70 years, 68% and 63% were men (vs. 59% in the general PD population; P < 0.05 for DBS), 73% and 63% had a partner (vs. 62% in the general PD population), and 73% and 71% had a qualifying education (vs. 63% in the general PD population; P < 0.05). Use of PD-related medication decreased significantly from 4 years before to 4 years after DAT. Eighty-one percent of the patients who started LCIG, alive 4 years later, had maintained this treatment. CONCLUSIONS: There is unequal access to DAT in the Danish regions, and political and social considerations are warranted to address structural and socioeconomic causes.

Density scaling of structure and dynamics of an ionic liquid.

Room temperature ionic liquids are salts with low melting points achieved by employing bulky and asymmetrical ions. The molecular design leads to apolar and polar parts as well as the presence of competing Coulomb and van der Waals interactions giving rise to nano-scale structure, e.g. charge ordering. In this paper we address the question of how these nano-scale structures influence transport properties and dynamics on different timescales. We apply pressure and temperature as control parameters and investigate the structure factor, charge transport, microscopic alpha relaxation and phonon dynamics in the phase diagram of an ionic liquid. Including viscosity and self diffusion data from literature we find that all the dynamic and transport variables studied follow the same density scaling, i.e. they all depend on the scaling variable Γ = ργ/T, with γ = 2.8. The molecular nearest neighbor structure is found to follow a density scaling identical to that of the dynamics, while this is not the case for the charge ordering, indicating that the charge ordering has little influence on the investigated dynamics.

Experimental Evidence for a State-Point-Dependent Density-Scaling Exponent of Liquid Dynamics.

A large class of liquids obey density scaling characterized by an exponent, which quantifies the relative roles of temperature and density for the dynamics. We present experimental evidence that the density-scaling exponent γ is state-point dependent for the glass formers tetramethyl-tetraphenyl-trisiloxane (DC704) and 5-polyphenyl ether (5PPE). A method is proposed that from dynamic and thermodynamic properties at equilibrium estimates the value of γ. The method applies at any state point of the pressure-temperature plane, both in the supercooled and the normal liquid regimes. We find that γ is generally state-point dependent, which is confirmed by reanalyzing data for 20 metallic liquids and two model liquids.

Isochronal superposition and density scaling of the α-relaxation from pico- to millisecond.

The relaxation dynamics in two van der Waals bonded liquids and one hydrogen-bonding molecular liquid are studied as a function of pressure and temperature by incoherent neutron scattering using simultaneous dielectric spectroscopy. The dynamics are studied in a range of alpha relaxation times from pico- to milliseconds, primarily in the equilibrium liquid state. In this range, we find that isochronal superposition and density scaling work not only for the two van der Waals liquids but also for the hydrogen-bonding liquid, though the density scaling exponent is much smaller for the latter. Density scaling and isochronal superposition are seen to break down for intra-molecular dynamics when it is separated in time from the alpha relaxation, in close agreement with previous observations from molecular dynamics simulations.

High-pressure cell for simultaneous dielectric and neutron spectroscopy.

In this article, we report on the design, manufacture, and testing of a high-pressure cell for simultaneous dielectric and neutron spectroscopy. This cell is a unique tool for studying dynamics on different time scales, from kilo- to picoseconds, covering universal features such as the α relaxation and fast vibrations at the same time. The cell, constructed in cylindrical geometry, is made of a high-strength aluminum alloy and operates up to 500 MPa in a temperature range between roughly 2 and 320 K. In order to measure the scattered neutron intensity and the sample capacitance simultaneously, a cylindrical capacitor is positioned within the bore of the high-pressure container. The capacitor consists of two concentric electrodes separated by insulating spacers. The performance of this setup has been successfully verified by collecting simultaneous dielectric and neutron spectroscopy data on dipropylene glycol, using both backscattering and time-of-flight instruments. We have carried out the experiments at different combinations of temperature and pressure in both the supercooled liquid and glassy state.

CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs.

Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal-neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.

Muscle interleukin-6 and fasting-induced PDH regulation in mouse skeletal muscle.

Fasting prompts a metabolic shift in substrate utilization from carbohydrate to predominant fat oxidation in skeletal muscle, and pyruvate dehydrogenase (PDH) is seen as a controlling link between the competitive oxidation of carbohydrate and fat during metabolic challenges like fasting. Interleukin (IL)-6 has been proposed to be released from muscle with concomitant effects on both glucose and fat utilization. The aim was to test the hypothesis that muscle IL-6 has a regulatory impact on fasting-induced suppression of skeletal muscle PDH. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and floxed littermate controls (control) were either fed or fasted for 6 or 18 h. Lack of muscle IL-6 elevated the respiratory exchange ratio in the fed and early fasting state, but not with prolonged fasting. Activity of PDH in the active form (PDHa) was higher in fed and fasted IL-6 MKO than in control mice at 18 h, but not at 6 h, whereas lack of muscle IL-6 did not prevent downregulation of PDHa activity in skeletal muscle or changes in plasma and muscle substrate levels in response to 18 h of fasting. Phosphorylation of three of four sites on PDH-E1α increased with 18 h of fasting, but was lower in IL-6 MKO mice than in control. In addition, both PDK4 mRNA and protein increased with 6 and 18 h of fasting in both genotypes, but PDK4 protein was lower in IL-6 MKO than in control. In conclusion, skeletal muscle IL-6 seems to regulate whole body substrate utilization in the fed, but not fasted, state and influence skeletal muscle PDHa activity in a circadian manner. However, skeletal muscle IL-6 is not required for maintaining metabolic flexibility in response to fasting.

CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.

Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)-binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.

The General Practitioner's Consultation Approaches to Medically Unexplained Symptoms: A Qualitative Study.

Background. The prevalence of medically unexplained symptoms (MUSs) in primary care is about 10-15%. The definition of MUS is descriptive and there are no specific diagnostic criteria for MUS in primary care. Furthermore, a general practitioner's (GP's) categorisation of patients with MUS shows large variation. The aim of the present study is to investigate how GPs employ the definition of MUS and how they manage patients with MUS in daily practice. Methods. With a grounded theory approach five focus group interviews with GPs were performed. The interviews addressed how GPs managed MUS and their reflections on the course and prognosis for MUS patients. Results. Consultations about MUS develop around the individual patient and usually include several appointments. We identified three different types of consultations: (1) "searching for a disease," (2) "going by the routine," and (3) "following various paths." These types of consultations spanned from a biomedical approach to an approach where multiple explanations were offered to explain the patient's problem. The choice of consultation types was influenced by the GP, the patient and contextual factors which, in turn, affected the diagnostic process. Conclusions. A diagnosis of MUS is contextually embedded and the diagnostic process is shaped by the consultation.

Are medically unexplained symptoms and functional disorders predictive for the illness course? A two-year follow-up on patients' health and health care utilisation.

OBJECTIVE: To investigate whether the general practitioners' (GP) diagnosis of medically unexplained symptoms (MUS) and/or the diagnosis functional disorders (FD) can predict the patients' 2-year outcome in relation to physical and mental health and health care utilisation. Furthermore, to identify relevant clinical factors which may help the GP predict the patient's outcome. METHOD: The study included 38 GPs and 1785 consecutive patients who presented a new health problem. The GPs completed a questionnaire on diagnosis for each patient. Patients completed the Common Mental Disorder Questionnaire (CMDQ) and the SF-36 questionnaire at baseline and after 24 months. A stratified sample of 701 patients was diagnosed with a psychiatric research interview. Data on health cost was obtained from national registers. RESULTS: A FD diagnosis following the research interview was associated with a decline in physical health (OR 3.27(95%CI 1.84-5.81)), but this was not the case with MUS diagnosed by the GP. MUS was associated with a poor outcome on mental health (OR 2.16 (95%CI 1.07-4.31)). More than 4 symptoms were associated with a poor outcome on physical health (OR 5.35 (95%CI 2.28-12.56)) and on mental health (OR 2.17(95%CI 1.02-4.59)). Neither FD nor MUS were associated with higher total health care use. However, FD (OR 2.31(95%CI 1.24-4.31)) and MUS (OR 1.98(95%CI 1.04-3.75)) was associated with increased cost in primary care. CONCLUSION: Our current diagnoses of MUS show limitations in their prediction of the patients' illness course. Although, the ICD-10 diagnoses of functional disorders was not developed for the primary care setting, our results indicate that some of its elements would be useful to bring in when rethinking the diagnosis for MUS in primary care, elements that are easily obtainable for the GP in a normal consultation. Our results may contribute to the construction of a more useful diagnostic for these patients in primary care.

Which is more important for outcome: the physician's or the patient's understanding of a health problem? A 2-year follow-up study in primary care.

OBJECTIVE: We sought to examine (1) whether the patients' and the family physicians' (FPs') beliefs about the nature of a health problem predict health outcomes and (2) whether the FPs were aware of their patients' beliefs. METHODS: A 2-year follow-up study of 38 FPs and 1131 patients presenting with well-defined physical disease (n=922) or medically unexplained symptoms (MUS) (n=209) according to the FPs was conducted. Before the consultation, patients categorized their health problem as being either physical or both physical and psychological. After the consultation, the FPs judged their patients' understanding of the health problem. Outcome measures were (1) patient satisfaction (seven-item Patient Satisfaction Consultation Questionnaire), (2) self-perceived mental and physical health (component summaries of the Medical Outcome Study's Short Form: SF-36) and (3) health care use extracted from patient registers. MAIN RESULTS: Patients with MUS according to the FPs and patients who believed that the nature of their health problem was both physical and psychological had higher health care use and worse self-rated health than patients in cases where both the FP and the patient had a physical understanding. Patients presenting MUS were more dissatisfied with the consultation than patients with well-defined physical disease. Overall, the FPs' perceptions of their patients' understanding were accurate in 82% of the consultations, but when the patients had a both physical and psychological understanding of their health problem, the FPs were right in only 26% of the consultations. CONCLUSIONS: Both FPs' diagnoses and patients' beliefs predict important health outcomes such as patient satisfaction, use of health care and self-rated health.

Personal use of hair dyes and temporary black tattoos in Copenhagen hairdressers.

BACKGROUND: Hairdressers are occupationally and personally exposed to hair dye substances and adverse reactions from the skin are well known. Currently, little is known about personal exposure to hair dye ingredients and temporary black tattoos. OBJECTIVES: To investigate hairdressers' professional and personal risk exposures and to compare the frequency of temporary tattoos among hairdressers and subjects from the general population. METHODS: A questionnaire was sent to 1679 Copenhagen hairdressers and 1063 (63.3%) responded; 3471 subjects from the general population in Copenhagen were asked about temporary black tattoos. RESULTS: Of the female hairdressers, 38.3% had coloured hair within the previous week. Adverse skin reactions to own hair dye were reported in 29.5%. In the hairdresser population, no significant association was observed between self-reported adverse skin reactions to hair dye and having had a temporary black tattoo when adjusted for sex, age, and atopy. A total of 19.0% of hairdressers (43.5% of apprentices) and 6.3% of participants from the general population had ever had a temporary black tattoo performed at one point. There were no differences in frequency of eczema after temporary tattooing between hairdressers and subjects in the general population. Almost all hairdressers (99.2%) used gloves for hair colouring, 51% for high/low lighting, 39.6% for perming and 21.1% used gloves for shampooing. CONCLUSIONS: In conclusion, skin reactions to hair colour are frequent among Copenhagen hairdressers. Temporary black tattoos were more frequent among hairdressers than in a sample of the general population and increased with decreasing age.

Improving the Classification of Medically Unexplained Symptoms in Primary Care

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Many patients in primary care complain of physical symptoms not attributable to any known conventionally defined disease, i.e. medically unexplained symptoms (MUS).Objectives: This paper aims to present the problems with our current classification of MUS in general practice and propose new criteria for the classification of Medically Unexplained Symptoms in a future edition of the International Classification of Primary Care (ICPC).Methods: Discussion of European classification systems in relation to current evidence about MUS in primary care. Results: At present, clinical care and research are hampered by the lack of a valid and reliable diagnostic classification of MUS. A particular problem in primary care is that the diagnostic category of somatoform disorders only includes persistent cases and therefore offers no opportunity for the classification of many patients with MUS in general practice. We propose new diagnostic criteria for MUS that can easily be integrated in a future edition of the ICPC. The criteria introduce mild to moderate MUS into the chapter of general and unspecified health problems if the patient has at least three MUS during an episode of care, whereas severe conditions are kept in the psychological chapter under the diagnoses applied until now. Conclusion: A diagnosis and classification of MUS is essential for the prediction of prognosis and the choice of appropriate care for these patients in general practice. It remains to be evaluated in epidemiologic research whether the proposed classification criteriafulfil this purpose (AU)

Synthesis of substituted 2-cyanoarylboronic esters.

The synthesis of substituted 2-cyanoarylboronic esters is described via lithiation/in situ trapping of the corresponding methoxy-, trifluoromethyl-, fluoro-, chloro-, and bromobenzonitriles. The crude arylboronic esters were obtained in high yields and purities and with good regioselectivities.