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Abstract Background Clinical guidelines are widely used to support clinical decision making, so they could also provide economic information about medical interventions to promote cost-conscious health care. We developed a new way to integrate economic information into the Finnish Current Care Guidelines. Methods Our development team consisted of clinical guideline specialists and health economists. We first looked at integration of economic information in clinical guidelines of other countries. Our key principle was that economic information should be integrated only to mutually exclusive medical interventions where the extensive choice of one the options will yield a significant cost differences on the national level. For the comparative effectiveness information of the interventions, we primarily looked for network meta-analyses. We then combined the effectiveness information presented as number needed to treat with prices or costs for the interventions and present the result as a cost per responder, which reflects both effectiveness and price or costs. Results We introduce a process to integrate and present the economic information of the selected interventions in tables in the Current Care Guidelines. Conclusions Our novel way to integrate economic information into the Current Care Guidelines is an effort to support cost-conscious clinical decision making to promote cost-effective health care in Finland. This process is general and could be used in clinical guidelines in other countries as well.

Protecting rivers and lakes from pollution is crucial for maintaining the health of aquatic ecosystems and ensuring the well-being of both wildlife and humans. Present study intends to examine the water quality of the Suna River (Eastern Fennoscandia in the European North of Russia) to assess the ecological risk. Widespread methods for assessing water quality based on macrozoobenthos and phytoperiphoton were applied. It was found that in conditions of ultra-fresh waters with high humus content, biotic indicators may indicate pollution of water bodies that do not actually experience significant anthropogenic impact. Ratings ranging from ‘poor’ to ‘excellent’ were obtained for different stations, reflecting the influence of natural features of different sections of the river. ‘Good’ water quality was noted at the river stones biotopes. In river gravel, sand and silt biotopes, as well as all lake biotopes, ‘mediocre’ water quality was found. The low anthropogenic income on the river catchment allows us to conclude that most indices for assessing water quality significantly underestimate the results in the natural conditions of Eastern Fennoscandia. Biotic indices EPT, BBI and EBI are most accurate for assessing the water quality of rivers and lakes in Eastern Fennoscandia. HIGHLIGHTS An assessment of the ecological state of the freshwater ecosystem in the North of Russia has been carried out.; Macrozoobenthos and periphyton can be indicators of the state of the environment.; The anthropogenic factor is important in the formation of a high-quality aquatic environment.; Water quality is determined by the degree of the impact on the ecosystem.; Very low water mineralization and high humus content make it difficult to determine the ecological status of rivers and lakes.;

Abstract The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. Plain Language Summary This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P

ABSTRACT Background X‐linked recessive type 3 Charcot–Marie–Tooth (CMTX3) is a rare subtype of childhood‐onset CMT. To date, all reported CMTX3 patients share a common founder 78 kb insertion from chromosome 8 into the Xq27.1 palindrome region. Methods We conducted patient–parent trio optical genome mapping (OGM) on a male patient presenting with clinically diagnosed Dejerine–Sottas disease for whom initial standard diagnostic genetic tests, including whole‐genome sequencing (WGS), yielded negative results. Results OGM analysis revealed a maternally inherited interchromosomal insertion from chromosome region 7q31.1 into Xq27.1. Coupled with manual reassessment of WGS data, this confirmed the molecular diagnosis of atypical CMTX3 and showed that the 122.4 kb inserted fragment contained DLD and partially LAMB1. Subsequent analyses confirmed that the rearrangement had arisen de novo in the proband's mother. Conclusion We report the second Xq27.1 rearrangement associated with CMTX3, providing novel clinical insights into its phenotypic and genotypic spectrum. Our findings highlight the importance of including genomic rearrangement analysis of Xq27.1 in standard diagnostic pipelines for childhood‐onset CMT. Given the overlap in polyneuropathy phenotypes resulting from insertions from chromosomes 7 and 8 into the same Xq27.1 palindrome region, the pathogenic mechanism underlying peripheral neuropathy in CMTX3 likely involves dysregulation of genes within this region.

Abstract Background Healthcare costs are rising worldwide. At the same time, a considerable proportion of care does not benefit or may even be harmful to patients. We aimed to explore attitudes towards low-value care and identify the most important barriers to the de-implementation of low-value care use in primary care in high-income countries. Methods Between May and June 2022, we email surveyed primary care physicians in six high-income countries (Austria, Finland, Greece, Italy, Japan, and Sweden). Physician respondents were eligible if they had worked in primary care during the previous 24 months. The survey included four sections with categorized questions on (1) background information, (2) familiarity with Choosing Wisely recommendations, (3) attitudes towards overdiagnosis and overtreatment, and (4) barriers to de-implementation, as well as a section with open-ended questions on interventions and possible facilitators for de-implementation. We used descriptive statistics to present the results. Results Of the 16,935 primary care physicians, 1,731 answered (response rate 10.2%), 1,505 had worked in primary care practice in the last 24 months and were included in the analysis. Of the respondents, 53% had read Choosing Wisely recommendations. Of the respondents, 52% perceived overdiagnosis and 50% overtreatment as at least a problem to some extent in their own practice. Corresponding figures were 85% and 81% when they were asked regarding their country’s healthcare. Respondents considered patient expectations (85% answered either moderate or major importance), patient’s requests for treatments and tests (83%), fear of medical error (81%), workload/lack of time (81%), and fear of underdiagnosis or undertreatment (79%) as the most important barriers for de-implementation. Attitudes and perceptions of barriers differed significantly between countries. Conclusions More than 80% of primary care physicians consider overtreatment and overdiagnosis as a problem in their country’s healthcare but fewer (around 50%) in their own practice. Lack of time, fear of error, and patient pressures are common barriers to de-implementation in high-income countries and should be acknowledged when planning future healthcare. Due to the wide variety of barriers to de-implementation and differences in their importance in different contexts, understanding local barriers is crucial when planning de-implementation strategies.

Abstract Evidence on the intergenerational continuity of loneliness and on potential mechanisms that connect loneliness across successive generations is limited. We examined the association between loneliness of (G0) parents (859 mothers and 570 fathers, mean age 74 years) and their children (G1) (433 sons and 558 daughters, mean age 47 years) producing 991 parent–offspring pairs and tested whether these associations were mediated through subjective socioeconomic position, temperament characteristics, cognitive performance, and depressive symptoms. Mean loneliness across parents had an independent effect on their adult children’s experienced loneliness (OR = 1.72, 95% CI 1.23–2.42). We also found a robust effect of mothers’ (OR = 1.64, 95% CI 1.17–2.29), but not of fathers’ loneliness (OR = 1.47, 95% CI 0.96–2.25) on offspring’s experienced loneliness in adulthood. The associations were partly mediated by offspring depressive (41–54%) and anxiety (29–31%) symptoms. The current findings emphasize the high interdependence of loneliness within families mediated partly by offspring’s mental health problems.

Interest in a particular subject is one central factor in preservice teachers' decision to become subject teachers. Interest in a subject can also become visible in preservice teachers' teaching and may consequently impact their students' interest in the subject. However, the interest of preservice teachers in their major and minor subjects has been scarcely addressed. In Finland, secondary school teachers usually study and teach two or three subjects. Major subjects are often chosen based on interest; however, the reasons for choosing a minor subject can vary. In this study, we examined the narratives of three preservice subject teachers regarding their interest in their minor and major subjects. They all studied mathematics, physics, and chemistry and revealed a much weaker interest in the minor subjects compared to the major subjects. Interestingly, our findings also reveal that preservice teachers' perceived strengths in a specific subject may not be as crucial to their interests, as has been suggested by prior research. We discuss the consequences of preservice teachers' weaker interest in certain subjects and provide recommendations for teacher education.

The potassium-chloride co-transporter 2, KCC2, is a neuron-specific ion transporter that plays a multifunctional role in neuronal development. In mature neurons, KCC2 maintains a low enough intracellular chloride concentration essential for inhibitory neurotransmission. During recent years, pathogenic variants in the KCC2 encoding gene SLC12A5 affecting the functionality or expression of the transporter protein have been described in several patients with epilepsy of infancy with migrating focal seizures (EIMFS), a devastating early-onset developmental and epileptic encephalopathy. In this study, we identified a novel recessively inherited SLC12A5 c.692G>A, p. (R231H) variant in a patient diagnosed with severe and drug-resistant EIMFS and profound intellectual disability. The functionality of the variant was assessed in vitro by means of gramicidin-perforated patch-clamp experiments and ammonium flux assay, both of which indicated a significant reduction in chloride extrusion. Based on surface immunolabeling, the variant showed a reduction in membrane expression. These findings implicate pathogenicity of the SLC12A5 variant that leads to impaired inhibitory neurotransmission, increasing probability for hyperexcitability and epileptogenesis.

IntroductionKeloids form as a pathological response to skin wound healing, and their etiopathology is poorly understood. Myofibroblasts, which are cells transformed from normal fibroblasts, are believed to contribute to pathological scar formation in wounds.MethodsWe carried out a double-blinded randomized controlled trial (RCT) comparing the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in treating keloids. A total of 43 patients with 50 keloids were treated with either intralesional TAC or 5-FU injections, and their clinical response was evaluated. Biopsies were collected before, during, and after injection therapy from the active border of a keloid. To understand the role of myofibroblasts in keloids, we conducted an immunohistochemical analysis to identify myofibroblasts [α-smooth muscle actin (αSMA)] from the biopsies. We first defined the three histologically distinct regions-superficial, middle, and deep dermis-in each keloid.ResultsWe then demonstrated that myofibroblasts almost exclusively exist in the middle dermis of the keloids as 80% of the cells in the middle dermis were αSMA positive. However, both the percentage of myofibroblasts as well as the area covered by them was substantially lower in the superficial and deep dermis than in the middle dermis of the keloids. Myofibroblasts do not predict the clinical response to intralesional injection therapies. There is no difference in the myofibroblast numbers in keloids or in the induced change in myofibroblasts between the responders and non-responders after treatment.DiscussionThis study demonstrates that myofibroblasts reside almost exclusively in the middle dermis layer of the keloids, but their numbers do not predict the clinical response to intralesional injection therapies in the RCT.

Abstract Thermal shift assay (TSA) with altered temperature has been the most widely used method for monitoring protein stability for drug research. However, there is a pressing need for isothermal techniques as alternatives. This urgent demand arises from the limitations of TSA, which can sometimes provide misleading ranking of protein stability and fail to accurately reflect protein stability under physiological conditions. Although differential scanning fluorimetry has significantly improved throughput in comparison to differential scanning calorimetry and differential static light scattering throughput, all these methods exhibit moderate sensitivity. In contrast, current isothermal chemical denaturation (ICD) techniques may not offer the same throughput capabilities as TSA, but it provides more precise information about protein stability and interactions. Unfortunately, ICD also suffers from limited sensitivity, typically in micromolar range. We have developed a novel method to overcome these challenges, namely throughput and sensitivity. The novel Förster Resonance Energy Transfer (FRET)-Probe as an external probe is highly applicable to isothermal protein stability monitoring but also to conventional TSA. We have investigated ICD for multiple proteins with focus on KRASG12C with covalent inhibitors and three chemical denaturants performed at nanomolar protein concentration. Data showed corresponding inhibitor-induced stabilization of KRASG12C to those reported by nucleotide exchange assay.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint

Abstract Background De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. Methods We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. Results We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). Conclusion De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. Trial registration OSF (Open Science Framework): https://osf.io/ueq32 .

Abstract Background Medial knee osteoarthritis (OA) is a common health problem resulting in knee pain and limiting patients’ physical activity. After failed conservative treatment, unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are possible surgical treatment options for this condition. There is a paucity of high-quality evidence in the literature comparing objective and subjective outcomes of these procedures. Also, there is no common agreement on whether these procedures provide comparable results in late-stage medial knee OA patients. Methods We will perform a prospective randomized controlled trial comparing HTO and UKA in patients with late-stage medial knee OA. 100 patients with isolated medial knee OA (KL III–IV) are assigned to either UKA (n = 50) or HTO (n = 50) procedure in patients 45–65 years of age. Our primary outcome will be KOOS5 at one year postoperatively. Secondary outcomes include OARSI physical assessment, length of stay, wearable activity watch, radiographs (OA progression according to Kellgren-Lawrence classification), patient-reported outcomes (KOOS subscales, pain visual analog scale [VAS], Lysholm, and Oxford knee scores), and adverse events (conversion to total knee arthroplasty, surgery-related complications, need for revision surgery) outcomes. Our hypothesis is that neither of the interventions is superior as measured with KOOS5 at 12 months. Ethics and dissemination The institutional review board of the Helsinki and Uusimaa Hospital District has approved the protocol. We will disseminate the findings through peer-reviewed publications. Trial registration ClinicalTrials.gov/TooloH NCT05442242. Registered on 7/1/2022.

Background: Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for major depressive disorder (MDD). Recent attempts to improve TMS efficacy by individually targeting DLPFC subregions that are functionally connected to the subgenual anterior cingulate cortex (sgACC) appear promising. However, sgACC covers only a small subset of core MDD-related areas. Further, fMRI connectivity of sgACC is poorly repeatable within subjects. Methods: Based on an fMRI database analysis, we first constructed a novel core network model (CNM), capturing voxelwise emotion regulation- and MDD-related DLPFC connectivity. Then, in a sample of 15 healthy subjects and 29 MDD patients, we assessed (i) within-subject repeatability of the DLPFC connectivity patterns computed from time segments of varying lengths of individual-level fMRI data and (ii) association of MDD severity with the individual DLPFC connectivity strengths. We extracted group-level connectivity strengths in CNM from individual DLPFC coordinates stimulated with neuronavigated TMS in a separate sample of 25 MDD patients. These connectivity strengths were then correlated with individual TMS efficacy. Results: Compared with sgACC connectivity, CNM increased intraindividual repeatability 5-fold. DLPFC connectivity strength from CNM was associated with MDD severity and TMS efficacy. While the locations of CNM-based individual TMS targets remained constant within individuals, they varied considerably between individuals. Conclusions: CNM increased repeatability of functional targeting to a clinically feasible level. The observed association of MDD severity and TMS efficacy with DLPFC connectivity supports the validity of the CNM. The interindividual differences in target locations motivate future individualized clinical trials leveraging the CNM.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value

Our pedagogic developing project, ImproStory, addresses improvisation and storytelling. We study how these two concepts could be applied in arts and crafts education for both primary and Kindergarten (daycare) teachers. The majority of our data consists of digital questionnaires in basic arts and crafts studies of primary pre-service teachers (N = 323). Additional data (portfolios) contain a group of Kindergarten and primary pre-service teachers with a focus in visual arts (N = 8). All data were collected at the University of Helsinki (Finland) during the academic year 2014-2015. According to our study, pre-service teachers consider improvisation and storytelling to be beneficial skills. They see developing them as necessary and useful. Experimenting and learning the approach appear to strengthen pre-service teachers' collaboration and allow them to build independence, trust, and self-confidence within arts and crafts education. In addition, improvisation and storytelling helps them to recognize their individual creative potential.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Background Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. Methods To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Results Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Conclusions Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Tutkimuksessa kuvataan etäkotihoidon omaksumista osaksi kotihoidon palvelutarjontaa ja etäkotihoidon toteuttamista työntekijöiden ja esihenkilöiden näkökulmasta. Aineisto kerättiin keväällä 2022 kahden ison kaupungin etäkotihoidossa verkkovälitteisillä haastatteluilla. Yhteensä haastateltiin yhdeksää etäkotihoitoa toteuttavaa työntekijää ja kolmea esihenkilöä (n=12). Yksi tutkijapari haastatteli toisen kaupungin esihenkilön yksilöhaastattelulla ja työntekijät parihaastattelulla, ja toinen pari toisen kaupungin esihenkilöt parihaastattelulla ja työntekijät ryhmähaastattelulla. Aineisto analysoitiin aineistolähtöisellä sisällön analyysillä. Työntekijöiden ja esihenkilöiden aineistot yhdistettiin analyysivaiheessa. Tulosten mukaan tekijät, jotka tukivat etäkotihoidon omaksumista ja toteuttamista osana kotihoidon palvelutarjontaa, olivat: keskitetty organisointitapa, yhteiset toimintatavat, palvelun tunnettavuuden lisääminen, kokemus palvelun hyödyllisyydestä ja työntekijöiden osaaminen. Johtopäätöksenä voidaan todeta, että työntekijät ja esihenkilöt kokivat etäkotihoidon omaksumisen ja toteuttamisen pääosin positiivisena ja asiakkaan tilannetta hyödyntävänä.

Abstract While sunlight may influence cognitive function through several pathways, associations of residential sunlight exposure with cognitive function are not well known. We evaluated associations of long-term residential sunlight exposure with cognitive function among a representative cohort of 1838 Finnish adults residing in Finland who underwent comprehensive cognitive assessment in midlife. We linked daily recordings of global solar radiation to study participants using residential information and calculated the average daily residential exposure to sunlight for four exposure time intervals: 2 months, 1 year, 2 years and 5 years prior to the date of the cognition assessment. Associations of the residential sunlight exposure with cognitive function were assessed using linear regression analyses adjusting for season, sex, age, and individual- and neighborhood-level socioeconomic characteristics. Greater average residential sunlight exposure over 2 and 5 years prior to the cognitive function assessment was associated with better global cognitive function (b = 0.13, 95% CI = 0.01, 0.25; b = 0.17, 95% CI = 0.05, 0.29, per 1 MJ/m2 difference in sunlight exposure), while no associations with global cognitive function were observed at shorter exposure time intervals. In domain-specific analyses, greater residential exposure to sunlight over 1, 2 and 5 years prior to the cognitive function assessment was associated with better performance on new learning and visual memory (b = 0.10, 95% CI = 0.00, 0.20; b = 0.16, 95% CI = 0.04, 0.28; b = 0.19, 95% CI = 0.08, 0.31) and sustained attention (b = 0.15, 95% CI = 0.05, 0.25; b = 0.18, 95% CI = 0.06, 0.30; b = 0.17, 95% CI = 0.05, 0.29), but worse performance on reaction time (b = − 0.12, 95% CI = − 0.22, − 0.02; b = -0.15, 95% CI = − 0.28, − 0.02; b = − 0.18, 95% CI = − 0.30, − 0.05). Residential sunlight exposure was not associated with executive function. These findings suggest long-term residential sunlight exposure may be an environmental factor influencing cognitive function among a cognitively healthy cohort residing in Northern Europe. Further studies in populations residing in different geographical locations are needed.

Academics have multiple identities, and their professional identities can sometimes be fragmented. This can lead to identity tensions and hinder their development as teachers. Our data consists of interviews with seven academics at a research-intensive university and the teaching portfolios created during their teaching practicums. All academics participated in 2 years of pedagogical studies, wherein teaching practicums played a central role. Their teacher identities developed significantly during the pedagogical studies. We examined the narratives two academics--Matti and Kari--that chronicled their development as teachers. Initially, Matti and Kari presented bias towards the pedagogical training. We found that the key features of their teaching practicums, such as a developmental project and reflexivity, facilitated the development of more holistic, relational identities. Our findings challenge some dominant views about academics' teacher identity development and argue for the need to redefine academics' teacher identity by taking into account the relational nature of the concept and the role of the research-teaching nexus. The study has an important implication for policy; for supporting holistic teacher-researcher development, developmental projects should be implemented as a vital part of pedagogical training.

The Ostrobothnia Depression Programme (ODP) was launched to implement two evidence-based treatments (EBTs), behavioural activation and motivational interviewing, and to study their effectiveness. We performed a mixed methods evaluation to extract organization- and programme-related knowledge crucial in sustaining and scaling up the desired programme outcomes. A cross-sectional mixed methods survey was conducted with the programme addressees 4-5 months after the end of the ODP. The realization of case consultation groups was analysed further by interviewing those responsible for them and referring to attendance lists. The results showed that the ODP succeeded in initiating the desired change in clinical practice. Case consultations and training videos intended as reinforcers were underutilized. Weaknesses in the implementation plan and conducting the implementation programme and effectiveness study simultaneously hampered achieving progress and jeopardized the maintenance of the implementation outcomes in the long term. The complete training intervention in the intended EBTs should comprise both workshops and non-optional case consultations. Means to decentralize the clinical support in everyday work should be elaborated in collaboration with the participating teams. It is recommended coaching team leaders to deploy evidence-based managerial practices for facilitation.

Abstract Background Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. Methods MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. Results Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). Conclusions De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. Registration OSF Open Science Framework hk4b2

Total hip arthroplasty (THA) is a common treatment for osteoarthritis and is also performed for other conditions, such as secondary arthritis due to developmental dysplasia of the hip. Various THA types may be complicated by osteolysis and an inflammatory pseudotumor due to an adverse reaction to metal debris. Rarely, THA has been associated with malignant tumors, but their causality remains unclear. In this case report, we describe a female patient with developmental dysplasia of the hip. She had undergone left metal-on-polyethylene THA, acetabular revision of the THA, and left total knee arthroplasty. In addition, she had a history of dyslipidemia and telangiectasia of the eyes, anemia, hiatal hernia, and pleuritis. A THA-associated mass (suspected to be a pseudotumor) had been detected during a previous hospital admission due to pleuritis. She was hospitalized due to swelling in her left lower limb, fatigue, and bruises. A clinical examination revealed anemia, thrombocytopenia, and growth of the suspected pseudotumor. Within 6 weeks, she presented with bleeding of the oral mucosa, hemoptysis, melena, severe thrombocytopenia that did not respond to treatment, elevated D-dimer and C-reactive protein levels, severe pain, increased osteolysis, and fractures around the THA. Infection or malignancy was suspected, but two trocar biopsies suggested an inflammatory pseudotumor. Since her anemia and thrombocytopenia were considered to have been caused by an inflammatory process within the suspected pseudotumor, her suspected pseudotumor and all THA components were surgically removed. However, she developed severe alveolar hemorrhaging and hypoxia and died 2 weeks after her surgery. Histopathological analysis of her surgical and autopsy samples revealed highly malignant angiosarcoma. Although individual cases of malignancies associated with THA have been reported, the literature lacks a clear association between THA and increased cancer risk. Most pseudotumors are non-malignant. The patient's case presented in this report exemplifies the challenges to the differential diagnosis of a THA-associated pseudotumor and rare angiosarcoma. Atypically rapid tumor growth, severe osteolysis, and deterioration in the general wellbeing suggest a malignant disease.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

Abstract Aims The purpose was to examine the prevalence and determinants of self‐reported eating problems in old home care clients, screened separately by a clinical nutritionist and a dental hygienist. Methods and Results The data came from the Nutrition, Oral Health and Medication (NutOrMed) study, the participants of which were ≥75‐year‐old home care clients living in Finland. The structured interviews were conducted at the participants' (n = 250) homes. Of the participants, 29% reported poor appetite, 20% had problems with chewing, and 14% had problems with swallowing when asked by a clinical nutritionist. Additionally, 18% reported oral health‐related eating problems when asked by a dental hygienist. Participants with continuous xerostomia (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0–9.0) or poor self‐reported oral health (OR: 4.3, 95% CI: 1.4–13.0) had a higher risk for problems with chewing when asked by a clinical nutritionist. Edentulous participants (OR: 3.5, 95% CI: 1.2–10.9) and participants with toothache or problems with dentures (OR: 10.3, 95% CI: 4.0–26.0) had a higher risk for oral health‐related eating problems when asked by a dental hygienist. Conclusion Eating problems are common in older adults, and interprofessional collaboration is required for their identification and alleviation.

Abstract While characteristics of psychosocial work environment have traditionally been studied separately, we propose an alternative approach that treats psychosocial factors as interacting elements in networks where they all potentially affect each other. In this network analysis, we used data from a prospective occupational cohort including 10,892 participants (85% women; mean age 47 years) and repeated measurements of seven psychosocial work characteristics (job demands, job control, job uncertainty, team climate, effort-reward imbalance, procedural justice and interactional justice) assessed in 2000, 2004, 2008 and 2012. Results from multilevel longitudinal vector autoregressive models indicated that job demands as well as interactional and procedural justice were most broadly associated with the subsequent perceptions of the work-related psychosocial factors (high out-Strength), suggesting these factors might be potentially efficient targets of workplace interventions. The results also suggest that modifying almost any of the studied psychosocial factors might be relevant to subsequent perceptions of effort-reward imbalance and interactional justice at the workplace.

Employability is an increasing concern for university students. Our survey set out to examine university students' perceptions of their employability and the ways in which these perceptions relate to positions that subsequently connect students to working life: students' self-representational position or "ability self", and students' life-historical positions such as chosen field of study, phase of degree and working life experience. The participants comprised a sample of students (N = 1819) from two Finnish universities, representing diverse fields of study. It was found that apart from the field of study, the perceived proximity to graduation and working life was associated with the perception of employability. Furthermore, a set of self-attributed capabilities was associated with students' perceptions of employability, particularly extroversion, ambitious competitiveness, mental strength and the desired characteristics of a good employee; however, the attribution of academic skills showed opposing effects. It was concluded that both self-representational and live-historical positions are part of the construction of students' optimism regarding their employability.