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Pilot experiments were conducted to assess the removal of organic micropollutants from biologically treated wastewater at a municipal wastewater treatment plant in Sweden. Powdered activated carbon (PAC) was combined with a low dose of ozone added directly before the PAC contact tank, enabling ozone to react simultaneously with the PAC and the wastewater contaminants. This combination of ozone and PAC was compared to PAC or ozone alone. The process, which included coagulation/flocculation and ballasted high-rate lamella sedimentation, proved to be both robust and efficient for the removal of micropollutants. The addition of 1.3 mg PAC/mg DOC resulted in a 73% average reduction of micropollutants. With the addition of 0.13 mg O3/mg DOC, the reduction increased to 83%, which was similar to the outcome with the addition of 2.6 mg PAC/mg DOC without ozone. The process configuration and operating conditions did not lead to any detectable bromate formation despite relatively high influent bromide levels. The estimated operating costs for combining PAC with a low dose of ozone were significantly lower than for applying a higher PAC dose. Thus, this way of combining PAC with ozone seems to have several advantages with respect to treatment efficiency and operation. HIGHLIGHTS Pilot trial for micropollutant removal from wastewater with PAC and ozone.; Ozone addition directly before the PAC volume.; Low dose of ozone decreased PAC consumption and operating costs.; No detectable bromate formation.;

Abstract Objective To investigate the associations between low education and risk of mental disorders, substance use disorders and self‐harm in different age‐groups. Methods All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed‐up for these disorders in health care registers 2001–2016. Subjects were stratified into four age‐groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models. Results Low education increased the risk of substance use disorders and self‐harm in all age‐groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism. Conclusion Low education is associated with risk of most mental disorders, substance use disorders and self‐harm in all age‐groups, but especially among those aged 28–50 years.

BackgroundDespite universal healthcare, socioeconomic differences in healthcare utilization (HCU) persist in modern welfare states. However, little is known of how HCU inequalities has developed over time. The aim of this study is to assess time trends of differences in utilization of primary and specialized care for the lowest (Q1) and highest (Q5) income quantiles and compare these to mortality.Methods and findingsUsing a repeated cross-sectional register-based study design, data on utilization of (i) primary; (ii) specialized outpatient; and (iii) inpatient care, as well as (iv) cause of death, were linked to family income and sociodemographic control variables (for instance, country of origin and marital status). The study sample comprised all individuals 16 years or older residing in Sweden any year during the study period and ranged from 7.1 million in year 2004 to 8.0 million year 2017. HCU and mortality for all disease as well as for the 5 disease groups causing most deaths were compared for the Q1 and Q5 using logistic regression, adjusting for sex, age, marital status, and birth country. The primary outcome measures were adjusted odds ratios (ORs), and regression coefficients of annual changes in these ORs log-transformed. Additionally, we conducted negative binominal regression to calculate adjusted rate ratios (RRs) comparing Q1 and Q5 with regard to number of disease specific healthcare encounters ≤5 years prior to death. In 2017, for all diseases combined, Q1 utilized marginally more primary and specialized outpatient care than Q5 (OR 1.07, 95% CI [1.07, 1.08]; p < 0.001, and OR 1.04, 95% CI [1.04, 1.05]; p < 0.001, respectively), and considerably more inpatient care (OR 1.44, 95% CI [1.43, 1.45]; p < 0.001). The largest relative inequality was observed for mortality (OR 1.78, 95% CI [1.74, 1.82]; p < 0.001). This pattern was broadly reproduced for each of the 5 disease groups. Time trends in HCU inequality varied by level of care. Each year, Q1 (versus Q5) used more inpatient care and suffered increasing mortality rates. However, utilization of primary and specialized outpatient care increased more among Q5 than in Q1. Finally, group differences in number of healthcare encounters ≤5 years prior to death demonstrated a similar pattern. For each disease group, primary and outpatient care encounters were fewer in Q1 than in Q5, while inpatient encounters were similar or higher in Q1. A main limitation of this study is the absence of data on self-reported need for care, which impedes quantifications of HCU inequalities each year.ConclusionsIncome-related differences in the utilization of primary and specialized outpatient care were considerably smaller than for mortality, and this discrepancy widened with time. Facilitating motivated use of primary and outpatient care among low-income groups could help mitigate the growing health inequalities.

Abstract Background Contractions of muscles in the calf induced by neuromuscular electrical stimulation (NMES) may prevent venous thromboembolism, help rehabilitation and optimize strength training, among other uses. However, compliance to NMES-treatment is limited by the use of suboptimal stimulation points which may cause discomfort and less effectivity. Knowledge of where one is most likely to find muscle motor points (MP) could improve NMES comfort and compliance. Aims To anatomically map the MPs of the calf as well as to calculate the probability of finding a MP in different areas of the calf. Material and methods On 30 healthy participants (mean age 37 years) anatomical landmarks on the lower limbs were defined. The location of the four most responsive MPs on respectively the medial and lateral head of gastrocnemius were determined in relation to these anatomical landmarks using a MP search pen and a pre-set MP search program with 3 Hz continuous stimulation (Search range:4.0–17.5 mA). The anatomy of the calves was normalized and subdivided into a matrix of 48 (6 × 8) smaller areas (3 × 3 cm), from upper medial to lower lateral, in order to calculate the probability of finding a MP in one of these areas. The probability of finding a MP was then calculated for each area and presented with a 95% confidence interval. Results The MP heatmap displayed a higher concentration of MPs proximally and centrally on the calf. However, there were wide inter-individual differences in the location of the MPs. The highest probability of finding a MP was in area 4, located centrally and medially, and in area 29, located centrolaterally and around the maximum circumference, both with 50% probability (95% CI: 0.31–0.69). The second highest probability of finding MPs was in areas 9, 10, 16, proximally and medially, all with 47% probability (95% CI: 0.28–0.66). These areas 4, 9, 10, 16 and 29 exhibited significantly higher probability of finding motor points than all areas with a mean probability of 27% and lower (p

Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell’s palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.

Abstract Background Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population. Methods We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression. Results Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress. Conclusions Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.

BackgroundThe COVID-19 pandemic is commonly believed to have increased common mental disorders (CMD, i.e., depression and anxiety), either directly due to COVID-19 contractions (death of near ones or residual conditions), or indirectly by increasing stress, economic uncertainty, and disruptions in daily life resulting from containment measure. Whereas studies reporting on initial changes in self-reported data frequently have reported increases in CMD, pandemic related changes in CMD related to primary care utilization are less well known. Analyzing time series of routinely and continuously sampled primary healthcare data from Sweden, Norway, Netherlands, and Latvia, we aimed to characterize the impact of the pandemic on CMD recorded prevalence in primary care. Furthermore, by relating these changes to country specific time-trajectories of two classes of containment measures, we evaluated the differential impact of containment strategies on CMD rates. Specifically, we wanted to test whether school restrictions would preferentially affect age groups corresponding to those of school children or their parents.MethodsFor the four investigated countries, we collected time-series of monthly counts of unique CMD patients in primary healthcare from the year 2015 (or 2017) until 2021. Using pre-pandemic timepoints to train seasonal Auto Regressive Integrated Moving Average (ARIMA) models, we predicted healthcare utilization during the pandemic. Discrepancies between observed and expected time series were quantified to infer pandemic related changes. To evaluate the effects of COVID-19 measures on CMD related primary care utilization, the predicted time series were related to country specific time series of levels of social distancing and school restrictions.ResultsIn all countries except Latvia there was an initial (April 2020) decrease in CMD care prevalence, where largest drops were found in Sweden (Prevalence Ratio, PR = 0.85; 95% CI 0.81–0.90), followed by Netherlands (0.86; 95% CI 0.76–1.02) and Norway (0.90; 95% CI 0.83–0.98). Latvia on the other hand experienced increased rates (1.25; 95% CI 1.08–1.49). Whereas PRs in Norway and Netherlands normalized during the latter half of 2020, PRs stayed low in Sweden and elevated in Latvia. The overall changes in PR during the pandemic year 2020 was significantly changed only for Sweden (0.91; 95% CI 0.90–0.93) and Latvia (1.20; 95% CI 1.14–1.26). Overall, the relationship between containment measures and CMD care prevalence were weak and non-significant. In particular, we could not observe any relationship of school restriction to CMD care prevalence for the age groups best corresponding to school children or their parents.ConclusionCommon mental disorders prevalence in primary care decreased during the initial phase of the COVID-19 pandemic in all countries except from Latvia, but normalized in Norway and Netherlands by the latter half of 2020. The onset of the pandemic and the containment strategies were highly correlated within each country, limiting strong conclusions on whether restriction policy had any effects on mental health. Specifically, we found no evidence of associations between school restrictions and CMD care prevalence. Overall, current results lend no support to the common belief that the pandemic severely impacted the mental health of the general population as indicated by healthcare utilization, apart from in Latvia. However, since healthcare utilization is affected by multiple factors in addition to actual need, future studies should combine complementary types of data to better understand the mental health impacts of the pandemic.

Abstract Background Neuromuscular electrical stimulation (NMES) may prevent muscle atrophy, accelerate rehabilitation and enhance blood circulation. Yet, one major drawback is that patient compliance is impeded by the discomfort experienced. It is well-known that the size and placement of electrodes affect the comfort and effect during high-intensity NMES. However, during low-intensity NMES the effects of electrode size/placement are mostly unknown. Therefore, the purpose of this study was to investigate how electrode size and pragmatic placement affect comfort and effect of low-intensity NMES in the thigh and gluteal muscles. Methods On 15 healthy participants, NMES-intensity (mA) was increased until visible muscle contraction, applied with three electrode sizes (2 × 2 cm, 5 × 5 cm, 5 × 9 cm), in three different configurations on quadriceps and hamstrings (short-transverse (ST), long-transverse (LT), longitudinal (L)) and two configurations on gluteus maximus (short-longitudinal (SL) and long-longitudinal (LL)). Current–density (mA/cm2) required for contraction was calculated for each electrode size. Comfort was assessed with a numerical rating scale (NRS, 0–10). Significance was set to p

Background A rise in mental illness is expected to follow the COVID-19 pandemic, which has also been projected to lead to a deep global economic recession, further adding to risk factors. Aims The aim of this review was to assess the impact of the COVID-19 pandemic and previous pandemics, epidemics and economic crises on mental health. Method Searches were conducted in PubMed, Web of Science, PsycINFO and Sociological Abstracts. We included studies of all populations exposed to the COVID-19 pandemic, and other similar pandemics/epidemics and economic crises, compared with non-exposed time periods or regions. The outcome was mental health. Results The 174 included studies assessed mental health impacts of the COVID-19 pandemic (87 studies), 2008 economic crisis (84 studies) and severe acute respiratory syndrome (SARS) epidemic (three studies). Outcomes were divided into affective disorders, suicides, mental healthcare utilisation and other mental health. COVID-19 pandemic studies were of lesser quality than those for the economic crisis or SARS epidemic. Most studies for all exposures showed increases in affective disorders and other mental health problems. For economic crisis exposure, increases in mental healthcare utilisation and suicides were also found, but these findings were mixed for COVID-19 pandemic exposure. This is probably because of quarantine measures affecting help-seeking and shorter follow-ups of studies of COVID-19 pandemic exposure. Conclusions Our findings highlight the importance of available, accessible and sustainable mental health services. Also, socioeconomically disadvantaged populations should be particular targets of policy interventions during the COVID-19 pandemic.

Abstract Body The H2020/PERISCOPE project, including 32 partners from European universities & agencies, began 1st November 2020 and will last 36 months. The overarching objectives of PERISCOPE are to map and analyse the unintended impacts of the COVID-19 outbreak; develop solutions and guidance for policymakers and health authorities on how to mitigate the impact of the outbreak; enhance Europe’s preparedness for future similar events; and reflect on the future multi-level governance in the health as well as other domains affected by the outbreak. During this session we will report about early lessons learnt from the mapping and assessments of the impacts of the COVID-19 outbreak on mental health at national and subnational level in the EU with respect to individuals, communities and societies. Further, we will comment on their comparability. The aim is to explore differences between countries regarding the occurrence of mental ill health, and especially the impact on vulnerable groups, and how this is related to exposure to SARS-CoV-2, differences in policies over time, and effects on the economy. We will reflect on the short- and long-term consequences on mental health and health inequalities, report on the ongoing development of holistic policy guidelines for health authorities & other authorities, and from the analysis of multilevel governance, at local, regional and national level, memberstate – EU-level, and EU - global governance level. PERISCOPE will continue collecting data and updating a common data ”Atlas”, which would lead the consortium to engage in modelling and experiments to provide “continuous nowcasting” of the outbreak. Disclosure No significant relationships.

Abstract Introduction The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown. Methods Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT). Results Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: −3.2, 95% confidence interval (CI): −5.5 to −0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00–1.04, p = .038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = −.41, p = .013). Conclusions Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist.

Camels are vital to food production in the drylands of the Horn of Africa, with milk as their main contribution to food security. A major constraint to camel milk production is mastitis, inflammation of the mammary gland. The condition negatively impacts milk yield and quality as well as household income. A leading cause of mastitis in dairy camels is Streptococcus agalactiae, or group B Streptococcus (GBS), which is also a commensal and pathogen of humans and cattle. It has been suggested that extramammary reservoirs for this pathogen may contribute to the occurrence of mastitis in camels. We explored the molecular epidemiology of GBS in camels using a cross-sectional study design for sample collection and phenotypic, genomic and phylogenetic analysis of isolates. Among 88 adult camels and 93 calves from six herds in Laikipia County, Kenya, GBS was detected in 20% of 50 milk samples, 25% of 152 nasal swabs, 8% of 90 oral swabs and 3% of 90 rectal swabs, but not in vaginal swabs. Per camel herd, two to four sequence types (ST) were identified using Multi Locus Sequence Typing (MLST). More than half of the isolates belonged to ST617 or its single-locus variant, ST1652, with these STs found across all sample types. Capsular serotype VI was detected in 30 of 58 isolates. In three herds, identical STs were detected in milk and swab samples, suggesting that extramammary sources of GBS may contribute to the maintenance and spread of GBS within camel herds. This needs to be considered when developing prevention and control strategies for GBS mastitis. The high nasal carriage rate, low recto-vaginal carriage rate, and high prevalence of serotype VI for GBS in camels are in stark contrast to the distribution of GBS in humans and in cattle and reveal hitherto unknown ecological and molecular features of this bacterial species.

The purpose of this study is to interpret and qualitatively characterise the content in some research articles and evaluate cases of possible difference in meanings of the gene concept used. Using a reformulation of Hirst's criteria of forms of knowledge, articles from five different sub-disciplines in biology (transmission genetic, molecular biology, genomics, developmental biology and population genetics) were characterised according to knowledge project, methods used and conceptual contexts. Depending on knowledge project, the gene may be used as a location of recombination, a target of regulatory proteins, a carrier of regulatory sequences, a cause in organ formation or a basis for a genetic map. Methods used range from catching wild birds and dissecting beetle larvae to growing yeast cells in 94 small wells as well as mapping of recombinants, doing statistical calculations, immunoblotting analysis of protein levels, analysis of gene expression with PCR, immunostaining of embryos and automated constructions of multi-locus linkage maps. The succeeding conceptual contexts focused around concepts as meiosis and chromosome, DNA and regulation, cell fitness and production, development and organ formation, conservation and evolution. These contextual differences lead to certain content leaps in relation to different conceptual schemes. The analysis of the various uses of the gene concept shows how differences in methodologies and questions entail a concept that escapes single definitions and "drift around" in meanings. These findings make it important to ask how science might use concepts as tools of specific inquiries and to discuss possible consequences for biology education.

From early childhood, Hanna, born with Spinal Muscular Atrophy II, has adhered to a standing posture for all her independent locomotion. Aim: To investigate why Hanna in childhood chose to stand and the meaning that standing holds for Hanna as an adult. Method: Single case study of a single person, Hanna, based on her contemporary statements as an adult about her lived experience from childhood, introduced in a phenomenological context and analysed using hermeneutics. Result: Standing gives Hanna access to bodily comfort in an active posture, influences how the world presents itself to her, how she presents herself to the world, and improves interacting with others. Conclusion: Although just a single case study, the findings may stimulate further research on the possible benefits of standing combined with independent locomotion from early childhood and the meaning it can hold for people with SMA II.

Abstract Background No previous research has been performed into neck pain among forklift operators. This is a common complaint among these workers, who number around 150,000 in Sweden and six million in Europe. The aim of the study was to examine long-term exposure to unnatural neck positions among forklift operators as a risk factor for neck pain. Methods A retrospective cohort study was conducted of all eligible employees at a high-level warehouse. Forklift operators and office workers answered an 18-page questionnaire comprising questions about joint pain, work tasks, work postures and year of start for all items. By using person years in the exposed and less-exposed groups before start of neck pain we were able to calculate Incident Rate ratios for various exposures. Results Forty nine percent of the forklift operators reported having experienced neck pain compared to 30 % of office workers. Being a forklift operator was associated with an increased risk of neck pain (OR = 5.1, 95% CI 1.4–18.2). Holding the head in an unnatural position resulted in significantly increased risks for neck pain, irrespective of type of position. The risks for neck pain remained after taking other ergonomic exposures and psychosocial aspects into consideration. Conclusions This is the first published study showing that forklift operators have an increased risk of neck pain. The results are therefore of significance for improving work schedules, the adjustment of work tasks for these workers and the design of the vehicles.

Abstract Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are characterized by hyper-sensitivity to threat, and reduced structural and functional connectivity between the amygdala and orbitofrontal cortex (OFC). Previous studies of CD have not taken account of ADs nor directly compared connectivity in the two disorders. We examined three groups of young women: 23 presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with neither disorder (ND). Participants completed clinical assessments and diffusion-weighted and resting-state functional MRI scans. The uncinate fasciculus was reconstructed using tractography and manual dissection, and structural measures extracted. Correlations of resting-state activity between amygdala and OFC seeds were computed. The CD + AD and AD groups showed similarly reduced structural integrity of the left uncinate compared to ND, even after adjusting for IQ, psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was associated with harm avoidance traits among AD-only women, and with the interaction of poor anger control and anxiety symptoms among CD + AD women. Groups did not differ in functional connectivity. Reduced uncinate integrity observed in CD + AD and AD-only women may reflect deficient emotion regulation in response to threat, common to both disorders, while other neural mechanisms determine the behavioral response.

Background and purpose — Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively. Patients and methods — This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living. Results — Patients with BMI > 26 had a lower mortality rate than those with BMI 26 was 2.6 (95% CI: 1.2–5.5) after adjustment for age, sex, and physical status. Patients with BMI > 26 were also more likely to return to independent living after the hip fracture (OR = 2.6, 95% CI: 1.4–5.0). Patients with BMI 26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture.

The Curtin Coaches program represents a dynamic outreach opportunity for pre-service teachers enrolled in their first year of study at Curtin University to engage with school-aged students as classroom tutors. Research has shown that cross-age tutoring experiences in schools can benefit both the students receiving support and those who tutor, particularly in settings where individuals are engaging in community support work. According to program feedback, participants were able to develop a range of profession-related skills such as relationship building and gain new knowledge such as understanding how students learn. These competencies are salient as they align with the newly implemented standards for graduate teachers. Understanding the benefits such outreach programs bring pre-service teachers is vital as the future of HEPPP funded programs such as the Curtin Coaches is uncertain but the importance of Work Integrated Learning is increasing.

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

Lena Flodin,1,2 Maria Sääf,3 Tommy Cederholm,4 Amer N Al-Ani,2,5 Paul W Ackermann,5,6 Eva Samnegård,7 Nils Dalen,7 Margareta Hedström2,51Department of Geriatric Medicine, Karolinska University Hospital Stockholm, Sweden; 2Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden; 3Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden; 4Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; 5Department of Orthopedics, Karolinska University Hospital, Stockholm, Sweden; 6Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 7Department of Clinical Science, Division of Orthopedics, Karolinska Institutet, Danderyd Hospital, Stockholm, SwedenBackground: After a hip fracture, a catabolic state develops, with increased bone loss during the first year. The aim of this study was to evaluate the effects of postoperative treatment with calcium, vitamin D, and bisphosphonates (alone or together) with nutritional supplementation on total hip and total body bone mineral density (BMD).Methods: Seventy-nine patients (56 women), with a mean age of 79 years (range, 61–96 years) and with a recent hip fracture, who were ambulatory before fracture and without severe cognitive impairment, were included. Patients were randomized to treatment with bisphosphonates (risedronate 35 mg weekly) for 12 months (B; n=28), treatment with bisphosphonates along with nutritional supplementation (40 g protein, 600 kcal daily) for the first 6 months (BN; n=26), or to controls (C; n=25). All participants received calcium (1,000 mg) and vitamin D3 (800 IU) daily. Total hip and total body BMD were assessed with dual-energy X-ray absorptiometry at baseline, 6, and 12 months. Marker of bone resorption C-terminal telopeptide of collagen I and 25-hydroxy vitamin D were analyzed in serum.Results: Analysis of complete cases (70/79 at 6 months and 67/79 at 12 months) showed an increase in total hip BMD of 0.7% in the BN group, whereas the B and C groups lost 1.1% and 2.4% of BMD, respectively, between baseline and 6 months (P=0.071, between groups). There was no change in total body BMD between baseline and 12 months in the BN group, whereas the B group and C group both lost BMD, with C losing more than B (P=0.009). Intention-to-treat analysis was in concordance with the complete cases analyses.Conclusion: Protein-and energy-rich supplementation in addition to calcium, vitamin D, and bisphosphonate therapy had additive effects on total body BMD and total hip BMD among elderly hip fracture patients. Keywords: hip fracture, nutritional supplementation, bisphosphonates, bone mineral density

The purpose of this study is to analyze variations in how the gene concept is used and conceived in different sub-disciplines in biology. An examination of the development of subject matter and the use of the gene concept in a common college biology textbook shows that the gene concept is far from presented in a consistent way. The study describes and categorizes five different gene concepts used in the textbook; the gene as a trait, an information-structure, an actor, a regulator and a marker. These conceptual differences are not dealt with in an explicit manner. This constitutes one of the sources for confusion when learning about genes and genetics.

Introduces the project on the European Public Relations Body of Knowledge (EBOK). Reviews proposals on the definition, dimensions, and domain of public relations. Confronts these with findings from EBOK. Presents ideas on how to bridge the differences. Proposes ideas for further investigation. (SG)

Theodor W. Adorno’s criticism of human beings’ domination of nature is a familiar topic to Adorno scholars. Its connection to the central relationship between art and nature in his aesthetics has, however, been less analysed. In the following paper, I claim that Adorno’s discussion of art’s truth content ('Wahrheitsgehalt') is to be understood as art’s ability to give voice to nature (both human and non-human) since it has been subjugated by the growth of civilization. I focus on repressed non-human nature and examine Adorno’s interpretation of Eduard Mörike’s poem ‘Mausfallen-Sprüchlein’ (Mousetrap rhyme). By giving voice to the repressed animal, Mörike’s poem manages to point towards the possibility of a changed relationship between mice and men, between nature and humanity, which is necessary in order to achieve reconciliation amongst humans as well. Abstrakt Theodor W. Adornos Kritik an der Naturbeherrschung ist ein Topos, der Adorno-Forschern geläufig ist. Weniger analysiert wurde die Beziehung dieser Kritik zum für seine Ästhetik zentralen Verhältnis zwischen Kunst und Natur. Im vorliegenden Aufsatz stelle ich die These auf, dass Adornos Diskussion des Wahrheitsgehalts von Kunst zu verstehen ist als Fähigkeit der Kunst, der (sowohl menschlichen als auch nicht-menschlichen) Natur eine Stimme zu verleihen, nachdem sie durch das Wachsen der Gesellschaft unterjocht wurde. Ich konzentriere mich auf die unterdrückte nicht-menschliche Natur und untersuche dazu Adornos Interpretation von Eduard Mörikes Gedicht „Mausfallen-Sprüchlein“. Es gibt dem unterdrückten Tier eine Stimme und kann so die Möglichkeit eines anderen Verhältnisses zwischen Mäusen und Menschen, zwischen Natur und Menschheit aufzeigen – einer Änderung, die auch notwendig ist, um eine Versöhnung unter den Menschen zu erreichen.

Although Adorno takes modern, autonomous art as the starting point for his aesthetics, this does not mean that his idea of art's truth content is restricted to the artworks of modernity. In the article, I wish to show that Adorno's discussion of art's truth content is intimately connected with its capacity to express the suffering that nature has undergone and still undergoes in the name of enlightenment. I focus on art's expression of the suffering of non-human nature, and particularly non-human animals. I examine the interpretation Adorno makes in Dialectic of Enlightenment of an episode from The Odyssey, to show that even an artwork before the modern conception of art can be said to have truth content. Few commentators have considered this, and those who have, have not recognized Adorno's conviction that what is significant in authentic artworks is their ability to give voice not only to repressed human nature but also to repressed non-human nature. Giving voice to suffering nature and animals is something that unites The Odyssey with subsequent artworks, such as Mahler's Third Symphony.Camilla Flodin has a PhD in Aesthetics from Uppsala University (2009). Her dissertation examines Theodor W. Adorno's ideas on the relationship between art, nature and truth. In autumn 2010, she was Visiting Scholar at the Department of Philosophy, Columbia University. She currently teaches Aesthetics at the Department of Philosophy, Uppsala University. She has published in Estetika: The Central European Journal of Aesthetics and several Swedish cultural journals (such as Glänta and Hjärnstorm).

A review of Geoff Boucher’s Adorno Reframed (London and New York: I. B. Tauris, 2013, 166 pp. ISBN 978-1-84885-947-0).

Human NUDT16 is a member of the NUDIX hydrolase superfamily. After having been initially described as an mRNA decapping enzyme, recent studies conferred it a role as an "housecleaning" enzyme specialized in the removal of hazardous (deoxy)inosine diphosphate from the nucleotide pool. Here we present the crystal structure of human NUDT16 both in its apo-form and in complex with its product inosine monophosphate (IMP). NUDT16 appears as a dimer whose formation generates a positively charged trench to accommodate substrate-binding. Complementation of the structural data with detailed enzymatic and biophysical studies revealed the determinants of substrate recognition and particularly the importance of the substituents in position 2 and 6 on the purine ring. The affinity for the IMP product, harboring a carbonyl in position 6 on the base, compared to purine monophosphates lacking a H-bond acceptor in this position, implies a catalytic cycle whose rate is primarily regulated by the product-release step. Finally, we have also characterized a phenomenon of inhibition by the product of the reaction, IMP, which might exclude non-deleterious nucleotides from NUDT16-mediated hydrolysis regardless of their cellular concentration. Taken together, this study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16.

The mechanisms causing cognitive problems in chronic pain patients are not well understood. We used the Stroop color word task (SCWT) to investigate distraction-induced analgesia, cognitive performance, and cerebral activation patterns in 29 fibromyalgia (FM) patients (mean age 49.8 years, range 25-64 years) and 31 healthy controls (HC) (mean age 46.3 years, range 20-63 years). In the first study, SCWT was used to investigate distraction-induced analgesia in FM patients. Two versions of the task were applied, one with only congruent color-word images and one with incongruent images. Pressure pain thresholds were assessed using a pressure algometer before, during, and following SCWT. In the second study, reaction times (RTs) were assessed and functional magnetic resonance imaging (fMRI) was used to investigate cerebral activation patterns in FM patients and HC during the SCWT. An event-related task mixing incongruent and congruent images was used. In study one, we found reduced pressure pain sensitivity during SCWT in both groups alike and no statistically significant differences were seen between the incongruent and congruent conditions. The study two revealed longer RTs during the incongruent compared to the congruent condition in both groups. FM patients had longer RTs than HC in both conditions. Furthermore, we found a significant interaction between group and congruency; that is, the group differences in RTs were more pronounced during the incongruent condition. This was reflected in a reduced activation of the caudate nucleus, lingual gyrus, temporal areas, and the hippocampus in FM patients compared to HC. In conclusion, we found normal pain inhibition during SWTC in FM patients. The cognitive difficulties seen in FM patients, reflected in longer RTs, were related to reduced activation of the caudate nucleus and hippocampus during incongruent SCWT, which most likely affected the mechanisms of cognitive learning in FM patients.

BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions. METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms. CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.

To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg) around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

The human SnoN is an oncoprotein that interacts with several transcription-regulatory proteins such as the histone-deacetylase, N-CoR containing co-repressor complex and Smad proteins. This study presents the crystal structure of the Dachshund homology domain of human SnoN. The structure reveals a groove composed of conserved residues with characteristic properties of a protein-interaction surface. A comparison of the 12 monomers in the asymmetric unit reveals the presence of two major conformations: an open conformation with a well accessible groove and a tight conformation with a less accessible groove. The variability in the backbone between the open and the tight conformations matches the differences seen in previously determined structures of individual Dachshund homology domains, suggesting a general plasticity within this fold family. The flexibility observed in the putative protein binding groove may enable SnoN to recognize multiple interaction partners.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.