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Abstract The methanol extract form the leaves of Phytolacca icosandra L., afforded the unprecedented artificial triterpenoid fatty acid ester 1 derived from the new natural triterpenoid phytolaccagenic acid 3-O-myristate (1a), along with the three known triterpenoids serjanic, acinosolic and phytolaccagenic acid (2 – 4). Their structures were stablished by HR-EI-MS, 1D and 2D NMR techniques. The possible mechanistic formation of 1 is proposed, and the in vitro toxicity of all compounds was assessed using the brine shrimp lethality assay (BSLA). Graphic Abstract

Three point bending tests on V-notched specimens machined from a component cast in EN-GJS 500-14 nodular iron solid solution strengthened by silicon have been carried out. The 3P bending tests were performed at different stroke speeds (10-3 ~ 102 mm/s). The resulting strain rates at the V notch varied in the range of 1·10-4 ~ 5,8 s-1. The fracture surface of 3P bending tests was quantified in terms of ductile and brittle fracture using Scanning Electron Microscope (SEM). EN-GJS 500-14 has an increased brittle behavior with increasing strain rate. Predominately ductile fracture was observed for the strain rates 1·10-4~4·10-2S-1. . At the strain rate of about 1 s-1 more significant change in ductile to brittle fracture is seen. The 3P bending tests at -15°C showed predominately brittle fracture for the strain rates investigated 3,6·10-2 ~ 2,3 s-1.

Atmospheric dual-band Scheimpflug lidar is demonstrated at 980 and 1550 nm. Signals are compared during three weather conditions, and the spatio-temporal resolution of the atmospheric structure is considered. The potential for aerosol classification is evaluated, and future directions are discussed.

Estudo transversal de base populacional sobre altura de crianças de 12 a 59 meses (n = 2.632) foi realizado em Porto Alegre, Brasil. Usou-se regressão linear multinível para investigar o efeito de condições sócio-econômicas, demográficas, de saúde e dos ambientes físico e social sobre a altura, medida em escores-z do padrão de altura para idade do National Center for Health Statisrics. A área de localização do domicílio foi classificada como bem e mal provida em infra-estrutura habitacional. A altura foi, em média, -0,18 escore-z, estando positivamente associada a escolaridade e qualificação ocupacional dos pais, renda, qualidade de moradia, idade materna, intervalo interpartal e peso de nascimento, e negativamente relacionada a prematuridade, número de menores de cinco anos no domicílio e hospitalização nos dois primeiros anos de vida. O efeito da educação materna foi o dobro nas áreas mal providas em infra-estrutura habitacional. O efeito positivo da qualificação ocupacional dos pais foi evidente apenas nas áreas mal providas. Provavelmente, a área de residência modifica o efeito das condições sócio-econômicas sobre o crescimento. Programas habitacionais e de saneamento são potencialmente úteis para diminuir o efeito de condições sócio-econômicas desfavoráveis sobre o crescimento da criança.

A dirhodanine-substituted benzothiadiazole compound has been synthesised using Knoevenagel condensation of a dialdehyde-substituted benzothiadiazole and rhodanine. The resulting compound was deep orange red in colour and shows a HOMO and LUMO levels of −5.61 and −3.85 eV respectively, which makes it suitable for applications such as acceptor for organic solar cells.

Abstract Background The aim of this study was to document the development of bilateral knee osteoarthritis over a 12 year period using a middle-aged population-based cohort with knee pain at inclusion. Methods One hundred and forty three patients aged 35 to 54 were recruited from a population based cohort of 279 subjects who had knee pain at baseline and assessed with clinical and radiographic data, with 5 and 12 year follow up. The data was analysed with regard to the development and progression of uni- and bilateral knee osteoarthritis over 12 years. A definition of KL = 1 was used to define radiographic disease. Results 24 of the 30 (80%) patients with unilateral disease at baseline developed bilateral disease after 12 years. At baseline 37 patients (26%) had bilateral disease, whereas that number increased to 65 (52%) at 5 years and 100 (70%) at the 12 year follow up. The most common pattern was medial compartment involvement in both knees. Six patients had lateral compartment disease in one knee and medial in the other whereas only two had lateral compartment disease bilaterally. Conclusions Bilateral knee osteoarthritis is very common with time, as the majority of sufferers will eventually develop radiographic disease in both knees. Clinicians need to be aware of the ‘joint at risk’ and researchers need to remember to account for both knees when assessing the relationship between physical function, pain and structural disease. The other knee should not be used for comparison, even if it appears to be normal at baseline.

Abstract Background Male infertility is an increasing problem in all domestic species including man. Localization and identification of genes involved in defects causing male infertility provide valuable information of specific events in sperm development. Sperm development is a complex process, where diploid spermatogonia develop into haploid, highly specialized spermatozoa. Correct expression and function of various genes and their protein products are required for production of fertile sperm. We have identified an infertility defect in Finnish Yorkshire boars caused by spermatogenic arrest. The aim of this study was to locate the disease associated region using genome wide screen with the PorcineSNP60 Beadchip and identify the causal mutation by candidate gene approach. Results In the Finnish Yorkshire pig population the spermatogenic arrest (SA) defect appears to be of genetic origin and causes severe degeneration of germ cells and total absence of spermatozoa. Genome wide scan with the PorcineSNP60 Beadchip localized the SA defect to porcine chromosome 12 in a 2 Mbp region. Sequencing of a candidate gene Tex14 revealed a 51 bp insertion within exon 27, which caused differential splicing of the exon and created a premature translation stop codon. The expression of Tex14 was markedly down regulated in the testis of a SA affected boar compared to control boars and no protein product was identified by Western blotting. The SA insertion sequence was also found within intron 27 in all analyzed animals, thus the insertion appears to be a possible duplication event. Conclusion In this study we report the identification of a causal mutation for infertility caused by spermatogenic arrest at an early meiotic phase. Our results highlight the role of TEX14 specifically in spermatogenesis and the importance of specific genomic remodeling events as causes for inherited defects.

Abstract Background An association between traffic air pollution and respiratory symptoms among children has been reported. However, the effects of traffic air pollution on asthma and wheeze have been very sparsely studied in areas with low traffic intensity in cold climate with poor dispersion. We evaluated the impact of vehicle traffic on childhood asthma and wheeze by objective exposure assessment. Methods As a part of the Obstructive Lung Disease in Northern Sweden (OLIN) studies, a questionnaire was sent to the families of all children attending first or second grade in Luleå (72,000 inhabitants) in Northern Sweden in 2006. The age of the children was 7-8 years and the participation rate was 98% (n = 1357). Skin prick tests were performed in 1224 (89%) children. The home addresses were given geographical coordinates and traffic counts were obtained from the local traffic authorities. A proximity model of average daily traffic and average daily heavy vehicle traffic within 200 meters from each participant's home address was used. The associations between traffic exposure and asthma and wheeze, respectively, were analysed in an adjusted multiple logistic regression model. Results Exposure to high traffic flows was uncommon in the study area; only 15% of the children lived within 200 meters from a road with a traffic flow of ≥8000 vehicles per day. Living closer than 200 meters from a road with ≥500 heavy vehicles daily was associated with current wheeze, odds ratio 1.7 (confidence interval 1.0-2.7). A dose-response relation was indicated. An increased risk of asthma was also seen, however not significant, odds ratio 1.5 (confidence interval 0.8-2.9). Stratified analyses revealed that the effect of traffic exposure was restricted to the non-sensitized phenotype of asthma and wheeze. The agreement between self-reported traffic exposure and objective measurements of exposure was moderate. Conclusions This study showed that already at low levels of exposure, vehicle traffic is related to an increased risk of wheeze among children. Thus, the global burden of traffic air pollution may be underestimated.

Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

Abstract Background Male infertility is an increasing problem in all domestic species including man. Localization and identification of genes involved in defects causing male infertility provide valuable information of specific events in sperm development. Correct condensation of the sperm head and development of the acrosome are required for fertile sperm. In the Finnish Yorkshire pig population a knobbed acrosome defect (KAD) has been reported which appears to be of genetic origin. In previous studies we have shown that a large number of affected spermatozoa have a cystic swelling anterior to the apical part of the acrosome. Results Characterization of the knobbed acrosome affected sperm revealed that both the acrosomal granules and chromatin are affected. This type of KAD appears to be a previously unknown and serious form of the defect. A genome wide scan with PorcineSNP60 Genotyping BeadChip defined the KAD associated region within 0.7 Mbp on porcine chromosome 15. Two genes, STK17b and HECW2, located within this region were sequenced. The expression of these genes appeared comparable in KA-affected and control boars. The known function of HECW2 in acrosome development highlighted this gene as a good candidate responsible for the KAD. One nonsynonymous SNP was identified within the HECW2 gene. However, as this mutation was found in homozygous state in individuals with normal sperm, this is not likely to be the causal mutation. Conclusions In this study we identified two candidate genes for a severe defect affecting both the sperm acrosome and chromatin that causes infertility. One of these genes, HECW2, plays an important role in ubiquitination, a prerequisite for chromatin remodelling and acrosome formation, highlighting the involvement of this gene in the knobbed acrosome defect and male infertility.

Abstract Background Glatiramer acetate (GA) and interferon-beta (INFb) are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS). Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL) in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. Methods 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32), fatigue (Fatigue Impact Scale [FIS]) and depressed mood (Beck Depression Inventory-Short Form [BDI-SF]) at baseline and 6 and 12 months after start of GA treatment. Results At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p < 0.001), not in the pre-treated group. At month 12 43% of treatment-naïve patients had improved HR-QoL (increase LMS-QoL score 3 or more points) (p < 0.001). Likewise, mean FIS scores were decreased at months 6 and 12 in the treatment-naïve group (p < 0.01), not in the pre-treated group. In both groups mean BDI-SF scores did not change. No demographic or clinical baseline factor was predictive of HR-QoL increase. HR-QoL changes were zero to negative for patients who had discontinued GA before month 12 (28.4% of patients). Conclusions In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue.

Abstract Background The FUS-DDIT3 fusion oncogene encodes an abnormal transcription factor that has a causative role in the development of myxoid/round-cell liposarcomas (MLS/RCLS). We have previously identified FLT1 (VEGFR1) as a candidate downstream target gene of FUS-DDIT3. The aim of this study was to investigate expression of FLT1 and its ligands in MLS cells. Methods HT1080 human fibrosarcoma cells were transiently transfected with FUS-DDIT3-GFP variant constructs and FLT1 expression was measured by quantitative real-time PCR. In addition, FLT1, PGF, VEGFA and VEGFB expression was measured in MLS/RCLS cell lines, MLS/RCLS tumors and in normal adiopocytes. We analyzed nine cases of MLS/RCLS and one cell line xenografted in mice for FLT1 protein expression using immunohistochemistry. MLS/RCLS cell lines were also analyzed for FLT1 by immunofluorescence and western blot. MLS/RCLS cell lines were additionally treated with FLT1 tyrosine kinase inhibitors and assayed for alterations in proliferation rate. Results FLT1 expression was dramatically increased in transfected cells stably expressing FUS-DDIT3 and present at high levels in cell lines derived from MLS. The FLT1 protein showed a strong nuclear expression in cells of MLS tissue as well as in cultured MLS cells, which was confirmed by cellular fractionation. Tissue array analysis showed a nuclear expression of the FLT1 protein also in several other tumor and normal cell types including normal adipocytes. The FLT1 ligand coding gene PGF was highly expressed in cultured MLS cells compared to normal adipocytes while the other ligand genes VEGFA and VEGFB were expressed to lower levels. A more heterogeneous expression pattern of these genes were observed in tumor samples. No changes in proliferation rate of MLS cells were detected at concentrations for which the kinase inhibitors have shown specific inhibition of FLT1. Conclusions Our results imply that FLT1 is induced as an indirect downstream effect of FUS-DDIT3 expression in MLS. This could be a consequence of the ability of FUS-DDIT3 to hijack parts of normal adipose tissue development and reprogram primary cells to a liposarcoma-like phenotype. The findings of nuclear FLT1 protein and expression of corresponding ligands in MLS and normal tissues may have implications for tissue homeostasis and tumor development through auto- or intracrine signaling.

Abstract Background Several studies have been published where sperm plasma membrane integrity correlated to fertility. In this study we describe a simple fluorometer-based assay where we monitored the fluorescence intensity of artificially membrane-ruptured spermatozoa with a fixed time staining with fluorescent DNA dyes. Methods Membrane-impermeant fluorescent dyes Hoechst 33258 (H258) and propidium iodide (PI) were used to measure the fluorescence of the nucleus in artificially membrane ruptured spermatozoa and membrane-permeant dye Hoechst 33342 (H342) was used to measure fluorescence of intact spermatozoa. The concentration of spermatozoa in insemination doses varied from 31.2 × 106/ml to 50 × 106/ml and the average value was 35 × 106/ml. Each boar was represented by three consecutive ejaculates, collected at weekly intervals. Nonreturn rate within 60 days of first insemination (NR %) and litter size (total number of piglets born) of multiparous farrowings were used as fertility measures. Results Sperm fluorescence intensity of H258 and H342, but not the fluorescence intensity of PI-stained spermatozoa correlated significantly with the litter size of multiparous farrowings, values being r = - 0.68 (P < 0.01) for H258, r = - 0.69 (P < 0.01) for H342 and r = - 0.38, (P = 0.11) for PI. Conclusions The increase in fluorescence values of membrane-ruptured H258 and unruptured H342-stained spermatozoa in boar AI doses can be associated with smaller litter size after AI. This finding indicates that the fluorescence properties of the sperm nucleus could be used to select for AI doses with greater fertilizing potential.

Abstract Background The DDIT3 gene encodes a transcription factor belonging to the CCAAT/enhancer binding protein (C/EBP) family. It is normally expressed at very low levels but is activated by cellular stress conditions and induces G1 arrest and, in some cell types, apoptosis. DDIT3 is found as a part of the fusion oncogene FUS-DDIT3 that is causal for the development of myxoid/round-cell liposarcomas (MLS/RCLS). Results In the present study, we searched for putative interaction partners of DDIT3 and the oncogenic FUS-DDIT3 among G1 cyclins and cyclin-dependent kinases. We found that FUS-DDIT3 and the normal DDIT3 bind CDK2. In addition, CDK2 showed an increased affinity for cytoskeletal proteins in cells expressing FUS-DDIT3 and DDIT3. Conclusions We conclude that DDIT3 binds CDK2 and that many of the observed biological effects of DDIT3 may involve interaction with CDK2.

Abstract Background The frontal lobe has been associated to a wide range of cognitive control functions and is also vulnerable to degeneration in old age. A recent study by Thomsen and colleagues showed a difference between a young and old sample in grey matter density and activation in the left middle frontal cortex (MFC) and performance on a dichotic listening task. The present study investigated this brain behaviour association within a sample of healthy older individuals, and predicted a positive correlation between performance in a condition requiring executive attention and measures of grey matter structure of the posterior left MFC. Methods A dichotic listening forced attention paradigm was used to measure attention control functions. Subjects were instructed to report only the left or the right ear syllable of a dichotically presented consonant-vowel syllable pair. A conflict situation appears when subjects are instructed to report the left ear stimulus, caused by the conflict with the bottom-up, stimulus-driven right ear advantage. Overcoming this processing conflict was used as a measure of executive attention. Thickness and volumes of frontal lobe regions were derived from automated segmentation of 3D magnetic resonance image acquisitions. Results The results revealed a statistically significant positive correlation between the thickness measure of the left posterior MFC and performance on the dichotic listening measures of executive attention. Follow-up analyses showed that this correlation was only statistically significant in the subgroup that showed the typical bottom-up, stimulus-driven right ear advantage. Conclusion The results suggest that the left MFC is a part of an executive attention network, and that the dichotic listening forced attention paradigm may be a feasible tool for assessing subtle attentional dysfunctions in older adults.

Abstract Background Normal aging involves a decline in cognitive function that has been shown to correlate with volumetric change in the hippocampus, and with genetic variability in the APOE-gene. In the present study we utilize 3D MR imaging, genetic analysis and assessment of verbal memory function to investigate relationships between these factors in a sample of 170 healthy volunteers (age range 46–77 years). Methods Brain morphometric analysis was performed with the automated segmentation work-flow implemented in FreeSurfer. Genetic analysis of the APOE genotype was determined with polymerase chain reaction (PCR) on DNA from whole-blood. All individuals were subjected to extensive neuropsychological testing, including the California Verbal Learning Test-II (CVLT). To obtain robust and easily interpretable relationships between explanatory variables and verbal memory function we applied the recent method of conditional inference trees in addition to scatterplot matrices and simple pairwise linear least-squares regression analysis. Results APOE genotype had no significant impact on the CVLT results (scores on long delay free recall, CVLT-LD) or the ICV-normalized hippocampal volumes. Hippocampal volumes were found to decrease with age and a right-larger-than-left hippocampal asymmetry was also found. These findings are in accordance with previous studies. CVLT-LD score was shown to correlate with hippocampal volume. Multivariate conditional inference analysis showed that gender and left hippocampal volume largely dominated predictive values for CVLT-LD scores in our sample. Left hippocampal volume dominated predictive values for females but not for males. APOE genotype did not alter the model significantly, and age was only partly influencing the results. Conclusion Gender and left hippocampal volumes are main predictors for verbal memory function in normal aging. APOE genotype did not affect the results in any part of our analysis.

Abstract Background Enteric antimicrobial peptides secreted from Paneth cells, including α-defensins (in mice named cryptdins), are key effector molecules of innate immunity in the small intestine. The importance of Paneth cells α-defensins emerged from studies of enteric bacterial infection in genetically modified mice, as well as from recent studies linking reduced levels of these α-defensins to Crohn's disease localized to the ileum. However, analysis of expression of Paneth cell α-defensins is incomplete. We therefore performed a comprehensive evaluation of the distribution of antimicrobial molecules along the mouse small intestinal tract to identify potential variations in regional expression. Results In conventionally reared mice, the repertoire of Paneth cell antimicrobials differs between duodenum and ileum. In contrast to the uniform expression of most Paneth cell antimicrobials, both cryptdin 4 and cryptdin-related sequences (CRS) 4C peptides were expressed at progressively increasing amounts (101- and 104-fold, respectively) comparing duodenum and ileum. In tissues other than the small intestine, expression of CRS peptides was noted in thymus and caecum. Most Paneth cell products were also produced in the small intestine of germ-free mice at levels similar to those in controls, however CRS4C and RegIIIγ had reduced levels in the former (3- and 8-fold, respectively). No significant changes in expression levels of Paneth cell antimicrobial peptides was observed after oral challenge with either Salmonella enterica serovar typhimurium or Listeria monocytogenes, supporting current notions on the constitutive nature of this defensive system. Conclusion The repertoire of antimicrobial peptides changes along the small intestinal tract, and a subset of these molecules are up-regulated upon colonization, but not in response to enteric bacterial pathogens. The changes detected upon colonization suggest that Paneth cell antimicrobial peptides may play an important role in commensal microbial homeostasis, in addition to their proposed role in protection against infection. In addition, the differential expression of CRS4C along the small intestine suggests mechanisms of regulation that are distinct from other Paneth cell derived antimicrobial peptides.

Abstract Background FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. Results FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. Conclusion Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.

Abstract Background Tyrosine kinase inhibitors (TKIs) have gained much attention in recent years as targeted agents for the treatment of a wide range of human cancers. We have investigated the effect of the TKIs gefitinib and vandetanib on tumor cell lines derived from Ewing sarcoma, a highly malignant tumor affecting bone and soft tissue in children and young adults. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR) and vandetanib selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2) with additional activity against VEGFR-3, EGFR and RET kinase receptors. Results Two Ewing sarcoma cell lines investigated showed high levels of nuclear EGFR expression as well as moderate expression in plasma membrane and cytoplasm. When treated with concentrations of 5 μM and more of either gefitinib or vandetanib, we observed a significant decrease in cell proliferation. However, there were no detectable changes in p44/42 MAPK and Akt-1 phosphorylation, or in the expression of cyclin D1 or c-Myc following gefitinib or vandetanib treatment. Conclusion We conclude that Ewing sarcoma tumor cell proliferation is not highly sensitive to inhibition of EGFR signaling alone or the simultaneous inhibition of VEGFR receptors, EGFR and RET kinase. Decreased tumor cell proliferation could be achieved with gefitinib and vandetanib, but only at higher doses where non-specific effects of the compounds may be overriding. As Ewing tumor cells do not seem to depend on EGFR and VEGFR pathways for survival, other key factors in the cellular signaling of Ewing sarcoma should be targeted in order to obtain a potent therapeutic response.

Abstract Background COMP (Cartilage oligomeric matrix protein) is a matrix protein, which is currently studied as a potential serum marker for cartilage processes in osteoarthritis (OA). The influence of physical exercise on serum COMP is not fully elucidated. The objective of the present study was to monitor serum levels of COMP during a randomised controlled trial of physical exercise vs. standardised rest in individuals with symptomatic and radiographic knee OA. Methods Blood samples were collected from 58 individuals at predefined time points before and after exercise or rest, one training group and one control group. The physical exercise consisted of a one-hour supervised session twice a week and daily home exercises. In a second supplementary study 7 individuals were subjected to the same exercise program and sampling of blood was performed at fixed intervals before, immediately after, 30 and 60 minutes after the exercise session and then with 60 minutes interval for another five hours after exercise to monitor the short-term changes of serum COMP. COMP was quantified with a sandwich-ELISA (AnaMar Medical, Lund, Sweden). Results Before exercise or rest no significant differences in COMP levels were seen between the groups. After 60 minutes exercise serum COMP levels increased (p < 0.001). After 60 minutes of rest the serum levels decreased (p = 0.003). Median serum COMP values in samples obtained prior to exercise or rest at baseline and after 24 weeks did not change between start and end of the study. In the second study serum COMP was increased immediately after exercise (p = 0.018) and had decreased to baseline levels after 30 minutes. Conclusion Serum COMP levels increased during exercise in individuals with knee OA, whereas levels decreased during rest. The increased serum COMP levels were normalized 30 minutes after exercise session, therefore we suggest that samples of blood for analysis of serum COMP should be drawn after at least 30 minutes rest in a seated position. No increase was seen after a six-week exercise program indicating that any effect of individualized supervised exercise on cartilage turnover is transient.

Abstract Background The thylakoid membrane of higher plant chloroplasts is made of membrane lipids synthesized in the chloroplast envelope. As the inner envelope membrane and the thylakoid are separated by the aqueous stroma, a system for transporting newly synthesized lipids from the inner envelope membrane to the thylakoid is required. Ultrastructural as well as biochemical studies have indicated that lipid transport inside the chloroplast could be mediated by a system similar in characteristics to vesicular trafficking in the cytosol. If indeed the chloroplast system is related to cytosolic vesicular trafficking systems, a certain degree of sequence conservation between components of the chloroplast and the cytosolic systems could be expected. We used the Arabidopsis thaliana genome and web-based subcellular localization prediction tools to search for chloroplast-localized homologues of cytosolic vesicular trafficking components. Results Out of the 28952 hypothetical proteins in the A. thaliana genome sequence, 1947 were predicted to be chloroplast-localized by two different subcellular localization predictors. In this chloroplast protein dataset, strong homologues for the main coat proteins of COPII coated cytosolic vesicles were found. Homologues of the small GTPases ARF1 and Sar1 were also found in the chloroplast protein dataset. Conclusion Our database search approach gives further support to that a system similar to cytosolic vesicular trafficking is operational inside the chloroplast. However, solid biochemical data is needed to support the chloroplast localization of the identified proteins as well as their involvment in intra-chloroplast lipid trafficking.

Background: The emergency medical service (EMS) addresses all chief complaints across all ages in various contexts. Children in EMS present a particular challenge due to their unique anatomical and physical properties, which require specific training that EMS clinicians often report lacking. This combination exposes children to incidents threatening patient safety. The most common method to highlight incidents is the incident reporting system. Studies have shown underreporting of such incidents, highlighting the need for multiple methods to measure and enhance patient safety in EMS for children. Thus, the aim of this study was to modify and adapt the current Ambulance TT for road-based EMS (ATT) to a pediatric version (pATT) with a guide containing definitions of triggers., Methods: The adaption of the ambulance trigger tool to a version suitable for children followed a stepwise manner, including (1) a review of previous literature to pinpoint areas of risk regarding patient safety among children in EMS. (2) Three sessions of expert panel discussions via video meetings were held to evaluate each trigger of the ATT in terms of clinical relevance, comprehensibility, language and areas of risk regarding patient safety among children in EMS. (3) Clinical use of the pATT along with Retrospective Record Review (RRR). (4) Calculation of Item-level validity index and positive predictive value (PPV) for each trigger. (5) calculate inter-rater reliability between two independent record reviewers., Results: The literature search revealed 422 respective 561 articles in Cinahl and Medline where headlines and abstracts were read to identify areas posing risks to patient safety in EMS for children. During the structured discussions, one trigger was added to the existing 19 derived from the ATT, and the trigger definitions were modified to suit children. The three most common triggers identified in the 900 randomly selected records were deviation from treatment guidelines (63.9%), incomplete documentation (48.3%), and the patient is non conveyed after EMS assessment (41.1%). The positive triggers were categorized into near miss (54.6%), no harm incident (5.8%), and harmful incident (0.4%). Inter-rater reliability testing showed excellent agreement., Conclusion: This study demonstrates the adaptation of an existing trigger tool (ATT) to one suitable for children. It also shows that the trigger tool, along with retrospective record review, is a feasible method to evaluate patient safety in EMS, thus complementing existing methods., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Swedish Ethical Review Authority, Sweden (Dnr 2021 − 01130). The review board waived the requirement for informed consent. The record review was conducted within each organisation using their approved systems for data management. The records were anonymized and given an ID number before being presented to the author. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aim: This qualitative study explored the lived experiences of the patients with microphthalmia and anophthalmia and their parents, focusing on the healthcare, school settings and daily life challenges to improve patient management., Methods: In-depth interviews were conducted in Stockholm, Sweden, from October 2022 to June 2023. Participants were recruited through the St Erik Eye Hospital database (2008-2022), and the data was analysed using reflexive thematic analysis., Results: The study included 15 patients (9 female and 6 male), with a median age of 21 years (range 15-31), and 1 parent per patient. Five key themes were identified from the parental interviews and three from the patient interviews. Both groups emphasised the need for improvements in healthcare, including better physician continuity, emotional support, information provision and prosthesis functionality. Families of those with severe bilateral visual impairment highlighted the need for additional school and daily life support. While some parents had future concerns, most patients viewed their condition as a natural part of life., Conclusion: Patients and parents shared insights on the psychosocial impact and suggested improvements in the healthcare and school settings, providing valuable guidance for enhancing care and management for this patient group., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Efforts to understand the relationship between socioeconomic status (SES) and health have expanded beyond traditional indicators of education, income, occupation, and wealth to individuals' own reports of where they stand. This more contemporary approach has enjoyed considerable success, in that self-reported SES standing, often measured on a ladder representing the entire U.S. socioeconomic hierarchy, is associated strongly with health even when traditional SES indicators are controlled. However, disparities in self-rated health across ladder measures typically are not assessed with regard to health behavior disparities. Here, we draw on two US national probability samples assessing diverse ladder reference groups, as well as a new ladder asking people to report how much respect, honor, or esteem they receive from other people. Respect or honor offers a distinct potential to measure social influence across circles of recognition. We find that U.S.-based ladder status is related to smoking currently or ever and to days of exercise. While friend, neighbor, and respect-based ladders do not relate to health behaviors net of U.S. ladder standing, they show relationships to ever smoking and physical activity, and self-rated health, in their own right. Physical activity accounts for 12-18% of self-rated health disparities by friend, neighbor, or country ladder status. Smoking and drinking do not robustly contribute to ladder-based disparities in self-rated health. Contrasting what is typically found for traditional SES measures, physical activity merits further research, as does the receipt of respect or honor. That status ladder health disparities go largely unexplained by behaviors suggests the potential roles of non-behavioral pathways including inflammation, hopelessness, or classism., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Emergency medical services (EMS) personnel must rapidly assess and transport patients with time-sensitive conditions to optimise patient outcomes. Serum lactate, a valuable in-hospital biomarker, has become more accessible in EMS settings through point-of-care (POC) testing. Although POC lactate levels are valuable in specific patient groups, its broader application in EMS remains unclear. This study assessed the additional predictive value of POC lactate levels in a general adult EMS population., Methods: This prospective observational study (March 2018 to September 2019) involved two EMS organisations in Västra Götaland, Sweden. Patients were triaged using the Rapid Triage and Treatment System (RETTS). POC lactate levels were measured using StatStrip Xpress devices. Non-consecutive patients who received EMS and were aged 18 years and above were available for inclusion if triaged into RETTS levels: red, orange, yellow, or green if respiratory rate of ≥ 22 breaths/min. Outcomes were adverse outcomes, including a time-sensitive diagnosis, sequential organ failure assessment (SOFA) score ≥ 2, and 30-day mortality. Statistical analyses included descriptive statistics, imputation, and regression models to assess the impact of the addition of POC lactate levels to a base model (comprising patient age, sex, presence of past medical conditions, vital signs, pain, EMS response time, assessed triage condition, and triage level) and a RETTS triage model., Results: Of 4,546 patients (median age 75 [57, 84] years; 49% male), 32.4% had time-sensitive conditions, 12.5% met the SOFA criteria, and 7.4% experienced 30-day mortality. The median POC lactate level was 1.7 (1.2, 2.5) mmol/L. Patients with time-sensitive conditions had higher lactate levels (1.9 mmol/L) than those with non-time-sensitive conditions (1.6 mmol/L). The probability of a time-sensitive condition increased with increasing lactate level. The addition of POC lactate marginally enhanced the predictive models, with a 1.5% and 4% increase for the base and RETTS triage models, respectively. POC lactate level as a sole predictor showed chance-only level predictive performance., Conclusions: Prehospital POC lactate assessment provided limited additional predictive value in a general adult EMS population. However, it may be beneficial in specific patient subgroups, emphasizing the need for its judicious use in prehospital settings., (© 2024. The Author(s).)

Background: Emergency Medical Services (EMS) are a unique setting because care for the chief complaint is given across all ages in a complex and high-risk environment that may pose a threat to patient safety. Traditionally, a reporting system is commonly used to raise awareness of adverse events (AEs); however, it could fail to detect an AE. Several methods are needed to evaluate patient safety in EMS. In this light, this study was conducted to (1) develop a national ambulance trigger tool (ATT) with a guide containing descriptions of triggers, examples of use, and categorization of near misses (NMs), no harm incidents (NHIs), and harmful incidents (HIs) and (2) use the ATT on randomly selected ambulance records., Methods: The ambulance trigger tool was developed in a stepwise manner through (1) a literature review; (2) three sessions of structured group discussions with an expert panel having knowledge of emergency medical service, patient safety, and development of trigger tools; (3) a retrospective record review of 900 randomly selected journals with three review teams from different geographical locations; and (4) inter-rater reliability testing between reviewers., Results: From the literature review, 34 triggers were derived. After removing clinically irrelevant ones and combining others through three sessions of structured discussions, 19 remained. The most common triggers identified in the 900 randomly selected records were deviation from treatment guidelines (30.4%), the patient is non conveyed after EMS assessment (20.8%), and incomplete documentation (14.4%). The positive triggers were categorized as a near miss (40.9%), no harm (3.7%), and harmful incident (0.2%). Inter-rater reliability testing showed good agreement in both sessions., Conclusion: This study shows that a trigger tool together with a retrospective record review can be used as a method to measure the frequency of harmful incidents, no harm incidents, and near misses in the EMS, thus complementing the traditional reporting system to realize increased patient safety., (© 2024. The Author(s).)

Republicans and conservatives report better self-rated health and well-being compared to Democrats and liberals, yet they are more likely to reside in geographic areas with heavy COVID-19 morbidity and mortality. This harmed health on "both sides" of political divides, occurring in a time of rapid sociopolitical upheaval, warrants the revisiting of psychosocial mechanisms linked to political health differences. Drawing on national Gallup data (early 2021), we find that predicted differences in health or well-being vary substantially by ideology, party, voting behavior, and policy beliefs, with model fit depending on how politics are measured. Differences in self-rated health, psychological distress, happiness, trouble sleeping, and delayed health care tend to reveal worse outcomes for Democrats or liberals. Such differences often are reduced to insignificance by some combination of mastery, meritocratic beliefs, perceived social support, and COVID-19-related exposures and attitudes. Policy beliefs predict health differences most robustly across outcomes and mechanism adjustments.

Objective: Hyponatremia is associated with considerable morbidity and mortality, but causal links have been difficult to establish. Here, we describe the establishment and representativeness of the Stockholm Sodium Cohort (SSC), designed to study etiologies and outcomes of hyponatremia., Study Design and Setting: All residents of Stockholm County undertaking at least one serum sodium test between 2005-2018 were included in the SSC. Individual-level test results from over 100 laboratory parameters relevant to hyponatremia were collected and linked to data on demographics, socioeconomic status, healthcare contacts, diagnoses and dispensed prescription medications using national registers., Results: A total of 1,632,249 individuals, corresponding to 64% of the population of Stockholm County, were included in the SSC. Coverage increased with advancing age, ranging from 32% in children and adolescents (≤18 years) to 97% among the oldest (≥80 years). The coverage of SSC included the vast majority of patients in Stockholm County diagnosed with diabetes mellitus (93%), myocardial infarction (98%), ischemic stroke (97%), cancer (85%), pneumonias requiring inpatient care (95%) and deaths (88%)., Conclusion: SSC is the first cohort specifically designed to investigate sodium levels in a large, population-based setting. It includes a wide range of administrative health data and laboratory analyses. The coverage is high, particularly among elderly and individuals with comorbidities. Consequently, the cohort has a large potential for exploration of various aspects of hyponatremia., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It is controversial how useful bioassays are for identifying the in vivo toxicity of hazardous environmental exposures. In this study, fruiting bodies of forest mushrooms (n = 46), indoor mold colonies (n = 412), fungal secondary metabolites (n = 18), xenobiotic chemicals such as biocides and detergents (n = 6), and methanol extracts of indoor dusts from urban buildings (n = 26) were screened with two different bioactivity assays: boar sperm motility inhibition (BSMI) and inhibition of cell proliferation (ICP) tests. For the forest mushrooms, the toxicity testing result was positive for 100% of poisonous-classified species, 69% of non-edible-classified species, and 18% of edible-classified species. Colonies of 21 isolates of Ascomycota mold fungal species previously isolated from water-damaged buildings proved to be toxic in the tests. Out of the fungal metabolites and xenobiotic chemicals, 94% and 100% were toxic, respectively. Out of the indoor dusts from moldy-classified houses (n = 12) and from dry, mold-free houses (n = 14), 50% and 57% were toxic, respectively. The bioassay tests, however, could not differentiate the samples from indoor dusts of moldy-classified buildings from those from the mold-free buildings. Xenobiotic chemicals and indoor dusts were more toxic in the BSMI assay than in the ICP assay, whereas the opposite results were obtained with the Ascomycota mold colonies and fungal secondary metabolites. The tests recognized unknown methanol-soluble thermoresistant substances in indoor settled dusts. Toxic indoor dusts may indicate a harmful exposure, regardless of whether the toxicity is due to xenobiotic chemicals or microbial metabolites.

Background: Working in rural areas involves tackling long distances and occasional lack of supportive resources. Ambulance nurses are faced with the responsibility of making immediate autonomous decisions and providing extended care to critically ill patients during prolonged ambulance transport to reach emergency medical facilities. This study aims to expose the experiences of ambulance nurses acting as primary caregivers for critically ill patients during lengthy ambulance transfers in rural regions., Method: Fifteen nurses employed in an ambulance service within sparsely populated rural areas were subjected to semi-structured interviews. The collected data underwent qualitative content analysis., Result: The analysis resulted in one overarching theme with two categories. The theme is 'Safety in the Professional Role,' and the two categories are 'Working in sparsely populated areas presents challenges' and 'Rare events: when routine cannot be established.' The findings suggest that working as an ambulance nurse in a rural setting poses various challenges that can be highly stressful. Delivering care to critically ill patients during extended ambulance transports requires the knowledge, experience, and careful planning of the healthcare provider in charge., Conclusions: The findings underscore the necessity for thorough planning and adaptable thinking when attending to critically ill patients during extended transport scenarios. The absence of supporting resources can render the task demanding. Nevertheless, participants reported an inherent tranquility that aids them in maintaining focus amid their responsibilities., (© 2024. The Author(s).)

Background: There is a lack of knowledge regarding the epidemiology of severe trauma assessed by Swedish emergency medical services (EMS)., Aim: To investigate the prevalence of trauma in Sweden assessed by EMS from a national perspective and describe patient demography, aetiology, trauma type, prehospital triage and clinical outcomes., Methods: Data from two national quality registries, the Swedish Ambulance Registry and the Swedish Trauma Registry (SweTrau) were collected from January 1 to December 31, 2019. Inclusion criteria were an Emergency Symptoms and Signs code equivalent to trauma in the Swedish Ambulance Registry and criteria fulfilled for SweTrau inclusion. Exclusion criteria were patients < 18 years old, those not transported to a hospital and those without a personal identification number., Results: In total, 53,120 patients with trauma were included (14% of primary EMS missions involving a personal identification number). Of those, 2,278 (4.3%) patients (median age: 45 years; 32% women) were reported in SweTrau to have severe or potentially severe trauma (penetrating: 7%, blunt: 93%). In terms of including all causes of trauma, the code for 'trauma alert activation' was most frequent (55%). The most frequent injury mechanism was an injury caused by a car (34%). Most (89%) cases were assigned Priority 1 (life-threatening condition) at the dispatch centre. 62% were regarded as potentially life threatening upon EMS arrival, whereas 29% were assessed as non-life-threatening. Overall, 25% of the patients had new injury severity scores > 15. 12% required invasive treatment, 11% were discharged with severe disability and the 30-day mortality rate was 3.6%., Conclusion: In this cross-sectional study, 14% of the primary EMS missions for one year were caused by trauma. However, only a small proportion of these cases are severe injuries, and the risk of severe disabilities and death appears to be limited. The most frequent aetiology of a severe trauma is injury caused by a car, and most severe traumas are blunt. Severe traumas are given the highest priority at the dispatch centre in the vast majority of cases, but nearly one-third of these cases are considered a low priority by the EMS nurse. The latter leaves room for improvement., (© 2024. The Author(s).)

Aims and Objectives: To explore the onset of sepsis based on patients' and family members' experiences., Background: Knowledge about the onset of sepsis is limited among patients and their families, which makes early recognition of sepsis difficult. Previous studies argue that their stories are important to recognising sepsis and reduced suffering and mortality., Design: A descriptive design with a qualitative approach was used., Methods: In total, 29 patients and family members participated in 24 interviews with open-ended questions, including five dyadic and 19 individual interviews. The interviews were conducted during 2021, and participants were recruited from a sepsis group on social media. A thematic analysis based on descriptive phenomenology was performed. The study followed the COREQ checklist., Findings: Two themes emerged from the experiences: (1) When health changes into something unknown, including the two subthemes; Bodily symptoms and signs being vague but still tangible and Feelings of uncertainty, and (2) Turning points when warnings signs are deemed as serious, including the two subthemes Passing borders when feeling out of control and Difficulties understanding the seriousness., Conclusions: Patients' and family members' stories of the onset of sepsis indicate that symptoms and signs appeared insidiously and then noticeably worsen. The symptoms and signs seemed not be attributed to sepsis; instead, there was uncertainty about what the symptoms and signs meant. It was mainly family members who possibly understood the seriousness of the disease., Implications for the Profession and Patient Care: Patients' experiences of their symptoms and signs and family members' unique knowledge of the patient, indicate that healthcare professionals should listen and try to understand what the patient and family members are telling and take their concerns seriously. How the condition appears, and family members' concerns are important pieces of the assessment to recognise patients with sepsis., Patient or Public Contribution: Patients and family members contributed to the data collected., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Background: Globally, injuries are a major health problem, and in Sweden, injuries are the second most common reason for ambulance dispatch. However, there is a knowledge gap regarding the epidemiology of injuries requiring assessment by emergency medical services (EMS) in Sweden. The aim of the present study was to describe the prehospital population with injuries that have been assessed and treated by EMS., Methods: A randomly selected retrospective sample was collected from 1 January through 31 December 2019 in a region in southwestern Sweden. Data were collected from ambulance and hospital medical records., Results: Among 153,724 primary assignments, 26,697 (17.4%) were caused by injuries. The study cohort consisted of 5,235 patients, of whom 50.5% were men, and the median age was 63 years. The most common cause of injury was low-energy fall (51.4%), and this was the cause in 77.8% of those aged > 63 years and in 26.7% of those aged ≤ 63 years. The injury mechanism was a motor vehicle in 8.0%, a motorcycle in 2.1% and a bicycle in 4.0%. The most common trauma location was the residential area (55.5% overall; 77.9% in the elderly and 34.0% in the younger group). In the prehospital setting, the most frequent clinical sign was a wound (33.2%), a closed fracture were seen in 18.9% and an open fracture in 1.0%. Pain was reported in 74.9% and 42.9% reported severe pain. Medication was given to 42.4% of patients before arrival in the hospital. The most frequent triage colour according to the RETTS was orange (46.7%), whereas only 4.4% were triaged red. Among all patients, 83.6% were transported to the hospital, and 27.8% received fracture treatment after hospital admission. The overall 30-day mortality rate was 3.4%., Conclusion: Among EMS assignments in southwestern Sweden, 17% were caused by injury equally distributed between women and men. More than half of these cases were caused by low-energy falls, and the most common trauma location was a residential area. The majority of the victims had pain upon arrival of the EMS, and a large proportion appeared to have severe pain., (© 2023. The Author(s).)

Purpose: To investigate the surgical and pharmacological management and outcomes of patients with cataract and concurrent uveitis., Methods: Data from the Swedish National Cataract Register, 2018-2019, were collected and analysed. Uveitic eyes were identified and eyes without uveitis were used as controls. Generalized estimating equations were used to adjust for intra-individual correlation., Results: The study included 719 eyes with and 256 360 without uveitis. The mean age was 66.0 ± 13.5 (standard deviation [SD]) years in the uveitis group and 74.3 ± 8.7 years in the control group (p < 0.001). Surgery was associated with more intraoperative difficulties in eyes with uveitis (27.0%) than in control eyes (7.1%; p < 0.001). Posterior capsule rupture/zonular complications were registered in nine eyes with uveitis (1.3%) and in 1464 eyes without uveitis (0.6%; p = 0.02). Hydrophilic acrylic intraocular lenses (uveitis 3.6%, controls 1.2%) and subconjunctival steroids (uveitis 17.4%, controls 6.1%) were more frequently used in eyes with uveitis (p < 0.001). post-operative best-corrected visual acuity (BCVA) was 0.16 ± 0.38 logarithm of the minimum angle of resolution (logMAR, mean ± SD) in eyes with uveitis (n = 52) and 0.08 ± 0.20 in control eyes (n = 14 489; p = 0.008)., Conclusion: In this large registry-based Swedish cohort study, the findings demonstrate that cataract surgery in patients with uveitis poses more challenges and requires special surgical precautions. Eyes with concurrent uveitis had worse BCVA prior to and following surgery. Despite the intraoperative challenges, the visual improvement was greater in the uveitic group., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Many digital health projects often stop in the pilot or test phase. Realisation of new digital health services is often challenging due to lack of guidelines for the step-by-step roll-out and implementation of the systems when changing work processes and procedures are needed. This study describes development of the Verified Innovation Process for Healthcare Solutions (VIPHS) - a stepwise model for digital health innovation and utilisation using service design principles. A multiple case study (two cases) involving participant observation, role play, and semi-structured interviews were conducted for the model development in prehospital settings. The model might be helpful to support realisation of innovative digital health projects in a holistic, disciplined, and strategic way.

Potential markers were sought to diagnose mold hypersensitivity. Indoor air condensed water and human macrophage THP-1 test were applied to evaluate the buildings. Basophil activation tests (BAT) were conducted and mold-specific immunoglobulins (IgE, IgG, IgA, and IgD) were measured in study subjects' serum and feces. Exposed subjects reported markedly more symptoms from occupational air than controls. Basophils from exposed subjects died/lost activity at 225 times lower concentrations of toxic extracts from the target building than recommended in the common BAT protocol. Fecal IgG and IgD levels against Acrostalagmus luteoalbus and Aspergillus versicolor produced receiver operating curves (ROC) of 0.928 and 0.916, respectively, when plotted against the inflammation marker MRP8/14. Assaying serum immunoglobulin concentrations against the toxic Chaetomium globosum (MTAV35) from another building, a test control, did not differentiate study individuals. However, if liver metabolism produced the same core molecule from other Chaetomium globosum strains, this would explain the increased response in fecal immunoglobulins in the exposed. The altered immunoglobulin values in the samples of exposed when compared to controls revealed the route of mold exposure. The toxicity of indoor air condensed water samples, BAT and serology confirmed the severity of symptoms in the target building's employees, supporting earlier findings of toxicity in this building.

Increasing evidence points to the salience of early life experiences in shaping health inequalities, but scant research has considered the role of institutional resources as buffers in this relationship. Health care systems in particular are an understudied yet important context for the generation of inequalities from childhood into adulthood. This research investigates associations between childhood disadvantage and adult morbidity and examines the role of health care system quality in this relationship. We also consider the role of adult socioeconomic status. We merge individual-level data on major disease (2014 European Social Survey) with nation-level health care indicators. Results across subjective and objective approaches to health care system quality are similar, indicating a reduced association between childhood socioeconomic status and adult disease in countries with higher quality health care. In total, our results reiterate the long-term influence of childhood disadvantage on health while suggesting health care's specific role as an institutional resource for ameliorating life course health inequalities.

Objective: Fetal alcohol spectrum disorders (FASD) is an umbrella term covering a spectrum of medical conditions caused by prenatal alcohol exposure. The FASD Eye Code is a new complementary ophthalmological diagnostic tool created to corroborate the complex FASD diagnosis. The aim of this work was to validate the FASD Eye Code by testing it on a second group of children diagnosed with FASD in a clinical setting., Methods and Analysis: A clinical study was carried out in a group of 21 children (13 males, 8 females, mean age 13.3 years) investigated for suspected FASD and a healthy sex-matched and age-matched control group (n=21). The participants underwent a detailed ophthalmological examination including visual perception problems (VPPs) assessment. Clinical examination results were compiled, and total scores were calculated according to the FASD Eye Code protocol (range 4-16)., Results: The median total score in the FASD group was 8. Eight individuals in the FASD group and none of the controls obtained a total score of ≥9 corresponding to 38% sensitivity and 100% specificity with an area under the curve of 0.90. A cut-off total score of ≥8 showed 52% sensitivity and 95% specificity. One individual in the FASD group versus 12 controls had a total score of 4, representing normal findings. No significant difference between the two groups regarding VPPs was seen., Conclusion: The FASD Eye Code can be used as a complementary diagnostic tool for FASD to assist in diagnosis and to detect ophthalmological abnormalities in individuals with suspected FASD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sport facilities represent extreme indoor environments due to intense cleaning and disinfection. The aim of this study was to describe the composition of the cultivated microbiota in dust samples collected in sport facilities during the COVID-19 pandemic. A dust sample is defined as the airborne dust sedimented on 0.02 m 2 within 28 d. The results show that the microbial viable counts in samples of airborne dust ( n = 9) collected from seven Finnish sport facilities during the pandemic contained a high proportion of pathogenic filamentous fungi and a low proportion of bacteria. The microbial viable counts were between 14 CFU and 189 CFU per dust sample. In seven samples from sport facilities, 20-85% of the microbial viable counts were fungi. Out of 123 fungal colonies, 47 colonies belonged to the potentially pathogenic sections of Aspergillus (Sections Fumigati , Nigri , and Flavi ). Representatives of each section were identified as Aspergillus fumigatus , A. flavus , A. niger and A. tubingensis. Six colonies belonged to the genus Paecilomyces. In six samples of dust, a high proportion (50-100%) of the total fungal viable counts consisted of these potentially pathogenic fungi. A total of 70 isolates were considered less likely to be pathogenic, and were identified as Aspergillus section Nidulantes , Chaetomium cochliodes and Penicillium sp. In the rural ( n = 2) and urban ( n = 7) control dust samples, the microbial viable counts were >2000 CFU and between 44 CFU and 215 CFU, respectively, and consisted mainly of bacteria. The low proportion of bacteria and the high proportion of stress tolerant, potentially pathogenic fungi in the dust samples from sport facilities may reflect the influence of disinfection on microbial communities.

Bad indoor air quality due to toxins and other impurities can have a negative impact on human well-being, working capacity and health. Therefore, reliable methods to monitor the health risks associated with exposure to hazardous indoor air agents are needed. Here, we have used transgenic Caenorhabditis elegans nematode strains carrying stress-responsive fluorescent reporters and evaluated their ability to sense fungal or chemical toxins, especially those that are present in moisture-damaged buildings. Liquid-based or airborne exposure of nematodes to mycotoxins, chemical agents or damaged building materials reproducibly resulted in time- and dose-dependent fluorescent responses, which could be quantitated by either microscopy or spectrometry. Thus, the C. elegans nematodes present an easy, ethically acceptable and comprehensive in vivo model system to monitor the response of multicellular organisms to indoor air toxicity.

Background: Those who suffer from eating disorders often experience serious impairment in quality of life and the majority never receive treatment. Treatment availability may be increased by implementing methods that demand less resources and are more easy accessible such as internet-based treatments, but knowledge about their effects is still insufficient. The study evaluated effects of two types of internet-based cognitive behavioral therapy and a structured day patient program, the latter being a standard treatment at an eating disorder clinic at the time for the study., Methods: 150 participants with bulimic eating disorders randomized to two types of internet based treatments (one pure online treatment and one based on a self-help guide in book-format) or an intensive 16-week day patient program. The number of participants that started treatment was 120 of which 98 in internet treatment and 22 in the day program. Outcome assessments were carried out at baseline, post treatment, and at one-year follow-up., Results: All treatments were associated with significantly improved eating disorder pathology, self-image, and clinical impairment. Although the day program generally showed larger effects, only one significant difference found was in diagnostic remission post treatment; 51 % of the participant was in remission in internet treatment and 88 % in the day program. At one-year follow-up, participants in the internet treatments had continued to improve, whereas in the day patient program the effect sustained. Internet treatment had a 36 % drop out rate, there were no dropouts found in the day program., Conclusions: All treatments were comparable in effect at follow-up, suggesting that internet treatment is a conceivable alternative to standard treatment. Internet treatment in a book-based format was also equally effective as a pure online format. Internet delivered cognitive behavioral treatment forms can make important contributions to achieve increased access to treatment for patients with bulimic eating disorders. Future research and clinical implications for internet delivered treatments in eating disorder services are discussed., Clinical Trial Registration: ISRCTN registry https://www.isrctn.com/ISRCTN44999017. The study was registered retrospectively., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Aims: To describe disparities in depressive symptoms and self-rated health with a novel, individual-level measure of subjective dignity administered before and during the COVID-19 pandemic., Methods: National survey data were collected across the United States by the Gallup Organization in Spring (2017) (n ​= ​1459) and again in Spring (2021) (n ​= ​1244). Subjective dignity is measured by self-reported perceptions of dignity in one's own life. Numerous demographic subgroups constructed across age, gender, race/ethnicity, education, income, urbanicity, labor force status, and political background are used to test for robustness of dignity-health associations within and across years., Results: All demographic subgroups studied reported numeric decreases in dignity from 2017 to 2021, with many of these decreases being both large and significant. With few group-year exceptions, subjective dignity relates to lower levels of depression and higher self-rated health, with dignity-depression associations significantly increasing from 2017 to 2021., Conclusions: Dignity, as a pluralistic moral concept, is purported to anchor legal, human rights, and cultural discourses on justice, equity, and social inclusion. This study provides timely, original evidence that subjective appraisals of dignity should be considered as a public health indicator, especially across periods of societal unrest or adversity. Given groupwise robustness of dignity-health associations as documented here, subgroup determinants and lay definitions of dignity may merit closer attention., (© 2022 The Authors.)

Background: Emergency department charge nurses are expected to oversee the quality of patient care, direct work, and the allocation of resources. The charge nurse is the unit's frontline leader, and he/she must have proper leadership training and support to carry out duties effectively. This study explores how charge nurses perceive their role in managing daily work and major incidents at the emergency department., Methods: A qualitative study based on focus group discussions using a semi-structured interview. Participants were 12 charge nurses from four Swedish emergency departments., Results: For data analysis, a systematic text condensation method was used. The analysis of data generated four categories: (1) Coping with chaos; (2) Need for further training; (3) Feeling of inadequacy; and (4) Lack of strategies., Conclusions: The study concluded that the emergency department charge nurse has frontline duties that are diverse, multifaceted, require good leadership qualities, and lack detailed job description. Charge nurses confront many challenges in their daily work, often with little training or the opportunity to develop in their professional. This study provides understanding of the concerns charge nurses hold about working as frontline leaders and that departmental heads must support the education and training of their charge nurses., Competing Interests: Conflicts of interest All the signing authors meet the requirements for authorship and they have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This prospective longitudinal study aimed to analyse the effect of partial wrist denervation on patient-reported outcomes, quality of life and objective function in symptomatic wrist osteoarthritis during the first year after surgery. Sixty consecutive patients underwent an anterior and posterior interosseous neurectomy during 2018-2020. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, EuroQol-5D-3L, pain at rest and on load, and objective function were assessed preoperatively and 3, 6 and 12 months postoperatively. Generalized estimating equations were used to analyse the effect on the outcome variables. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation and pain scores improved significantly postoperatively with no decline over time, but no patient reported outcome measure reached the minimal clinically important difference. Quality of life, strength and range of motion did not improve. We found no complications. Seventeen patients needed further surgery during the study period. More studies are needed to evaluate whether denervation is truly effective or not. Level of evidence: II.

This study aimed to assess the outcomes after simple trapeziectomy and trapeziectomy with ligament reconstruction and/or tendon interposition based on data in the Swedish national healthcare quality registry for hand surgery (HAKIR). Six-hundred and fifty thumbs were included, and 265 were assessed up to 12 months after operation. There was significant and clinically relevant improvement in patient-reported measures (pain on load, pain on motion without load, pain at rest, stiffness, weakness, and ability to perform activities of daily living and the Quick Disabilities of the Arm, Shoulder and Hand score) and objective measures (strength and thumb mobility) at 3 and 12 months for all procedures. The use of the abductor pollicis longus tendon had better improvement in some respects compared with the use of flexor carpi radialis or extensor carpi radialis tendons. However, overall, the use of a tendon adjuncts yielded no better outcomes than simple trapeziectomy. Level of evidence: III.

Background: Patients who call for emergency medical services (EMS) due to abdominal pain suffer from a broad spectrum of diseases, some of which are time sensitive. As a result of the introduction of the concept of 'optimal level of care', some patients with abdominal pain are triaged to other levels of care than in an emergency department (ED). We hypothesised that it could be challenging in a patient safety perspective., Aim: This study aims to describe consecutive patients who call for EMS due to abdominal pain and are triaged to self-care by EMS clinicians., Methods: This was an observational study performed in an EMS organisation in Western Sweden during 2020. The triage tool Rapid Emergency Triage and Treatment System (RETTS), which included Emergency Signs and Symptom (ESS) codes, was used to find medical records where patients with abdominal pain have been triaged to self-care and 194 patients was included in the study., Results: Of total 48,311 ambulance missions, A total of 1747 patients were labelled with ESS code six (abdominal pain), including 223 (12.8%) who were given the code for self-care and 194 who were further assessed by the research group. Of these patients, 32 (16.3%) had a return visit within 96 hours due to the same symptoms and 11 (5.6%) were hospitalised. In six of these patients, the EMS triage was evaluated retrospectively and assessed as inappropriate. These patients had a final diagnosis of ruptured abdominal aneurysm (n = 1), acute appendicitis with peritonitis (n = 2) and acute pancreatitis (n = 3). All these patients required extensive evaluation and different treatments, including acute surgery, antibiotics and fluid therapy., Conclusion: Amongst the 1747 patients assessed by EMS due to abdominal pain, 223 (12.8%) were triaged to self-care. Of the 194 patients who were further assessed, 16.3% required a return visit to the ED within 96 hours and 5.6% were hospitalised. Six patients had obvious time-sensitive conditions. Our study highlights the difficulties in the early assessment of abdominal pain and the requirement for an accurate decision support tool., (© 2022. The Author(s).)