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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., (© 2023 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Background: Despite 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 Findings: Using 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., Conclusions: Income-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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Flodin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Background: The 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., Methods: For 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., Results: In 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., Conclusion: Common 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Flodin, Sörberg Wallin, Tarantino, Cerchiello, Mladá, Kuklová, Kondrátová, Parimbelli, Osika, Hollander and Dalman.)

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.

Introduction and Aims: The gender difference in alcohol use seems to have narrowed in the Nordic countries, but it is not clear to what extent this may have affected differences in levels of harm. We compared gender differences in all-cause and cause-specific alcohol-attributed disease burden, as measured by disability-adjusted life-years (DALY), in four Nordic countries in 2000-2017, to find out if gender gaps in DALYs had narrowed., Design and Methods: Alcohol-attributed disease burden by DALYs per 100 000 population with 95% uncertainty intervals were extracted from the Global Burden of Disease database., Results: In 2017, all-cause DALYs in males varied between 2531 in Finland and 976 in Norway, and in females between 620 in Denmark and 270 in Norway. Finland had the largest gender differences and Norway the smallest, closely followed by Sweden. During 2000-2017, absolute gender differences in all-cause DALYs declined by 31% in Denmark, 26% in Finland, 19% in Sweden and 18% in Norway. In Finland, this was driven by a larger relative decline in males than females; in Norway, it was due to increased burden in females. In Denmark, the burden in females declined slightly more than in males, in relative terms, while in Sweden the relative decline was similar in males and females., Discussion and Conclusions: The gender gaps in harm narrowed to a different extent in the Nordic countries, with the differences driven by different conditions. Findings are informative about how inequality, policy and sociocultural differences affect levels of harm by gender., (© 2020 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: Psychopathic traits vary dimensionally in the population and are associated with multiple negative outcomes. The impaired integration theory (IIT) proposes that psychopathic traits are associated with abnormal neural network topology, such that disturbed integration of neural networks results in a self-perpetuating impairment in rapid integration and learning from multiple components of information. The IIT is based on findings from male offenders presenting high scores on all psychopathic traits. The present study investigated whether IIT predictions of topology abnormalities were associated with psychopathic traits, measured dimensionally, in young adult women with subsyndromal scores., Methods: Seventy-three women, with an average age of 25 years, were assessed using the Psychopathy Checklist-Revised and completed resting-state magnetic resonance imaging. Preprocessed time series from 90 anatomical regions were extracted to form connectivity matrices and used to calculate network topology based on graph theory. Correlations between total psychopathy and factor scores with both the raw connectivity matrix and global and local graph theory measures were computed., Results: Total psychopathy scores and behavioral factor scores were related to connectivity between several pairs of regions, primarily limbic/paralimbic. Psychopathic traits were not associated with global topology measures. Topology abnormalities, robust across network formation thresholds, were found in nodes of the default mode network and in hubs connecting several resting-state networks., Conclusions: IIT predictions of abnormal topology of hubs and default mode network nodes with dimensionally measured psychopathic traits were confirmed in a sample of young women. Regional abnormalities, accompanied by preserved global topology, may underlie context-specific abnormal information processing and integration., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The Stroop colour word test (SCWT) has been widely used to assess changes in cognitive performance such as processing speed, selective attention and the degree of automaticity. Moreover, the SCWT has proven to be a valuable tool to assess neuronal plasticity that is coupled to improvement in performance in clinical populations. In a previous study, we showed impaired cognitive processing during SCWT along with reduced task-related activations in patients with fibromyalgia. In this study, we used SCWT and functional magnetic resonance imagingFMRI to investigate the effects of a 15-week physical exercise intervention on cognitive performance, task-related cortical activation and distraction-induced analgesia (DIA) in patients with fibromyalgia and healthy controls. The exercise intervention yielded reduced fibromyalgia symptoms, improved cognitive processing and increased task-related activation of amygdala, but no effect on DIA. Our results suggest beneficial effects of physical exercise on cognitive functioning in FM., (© 2017 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

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.

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 (VO 2 -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, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) 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 VO 2 -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 VO 2 -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.

Background: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA., Methods: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity., Results: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters., Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.

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.

The neuronal circuitry that supports voluntary changes in eye position in tasks that require attention-driven oculo-motor control is well known. However, less is known about the neuronal basis for eye control during visual fixation. This, together with the fact that visual fixation is one of the most commonly used baseline conditions in resting-state functional magnetic resonance imaging (fMRI) studies, prompted us to conduct a study in which we employed resting-state fMRI and concurrent recordings of eye gaze to investigate the relationship between spontaneous changes in eye position during passive visual fixation and intrinsic brain activity. As a control experiment, we recorded fMRI brain activity related to cued voluntary vertical and horizontal changes in eye position in a block-related task-evoked fMRI experiment. Our results for the voluntarily performed changes in eye position elicited brain activity in the bilateral occipitotemporal cortex, supplementary motor cortex and frontal eye fields. In contrast, we show that slow fluctuations in eye position during passive visual fixation are linked to intrinsic brain activity, foremost in midline cortical brain regions located in the posteromedial parietal cortex and the medial prefrontal cortex, brain regions that act as core cortical hubs in the brain's default mode network. Our results suggest that subconscious and sustained changes in behavior are tied to intrinsic brain activity on a moment-by-moment basis., (© 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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.

Fibromyalgia (FM) is a syndrome characterized by chronic pain without known peripheral causes. Previously, we have reported dysfunctional pain inhibitory mechanisms for FM patients during pain administration. In this study we employed a seed correlation analysis, independent component analysis (ICA), and an analysis of fractional amplitude of low frequency fluctuations (fALFF) to study differences between a cohort of female FM patients and an age- and sex-matched healthy control group during a resting-state condition. FM patients showed decreased connectivity between thalamus and premotor areas, between the right insula and primary sensorimotor areas, and between supramarginal and prefrontal areas. Individual sensitivity to painful pressure was associated with increased connectivity between pain-related regions (e.g., insula and thalamus) and midline regions of the default mode network (including posterior cingulate cortex and medial prefrontal cortex) among patients and controls. However, neither ICA nor fALFF revealed any group differences. Our findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain during rest reflect an impaired central mechanism of pain modulation in FM. Weaker coupling between pain regions and prefrontal- and sensorimotor areas might indicate a less efficient system level control of pain circuits. Moreover, our results show that multiple, complementary analytical approaches are valuable for obtaining a more comprehensive characterization of deviant resting-state activity. In conclusion, our findings show that FM primarily is associated with decreased connectivity, for example, between several pain-related areas and sensorimotor regions, which could reflect a deficiency in pain regulation.

Pharmacological functional brain imaging has traditionally focused on neuropharmacological modulations of event-related responses. The current study is a randomized, cross-sectional resting-state functional magnetic resonance imaging study where a single dose of commonly prescribed amounts of either benzodiazepine (oxazepam), L-dopa, or placebo was given to 81 healthy subjects. It was hypothesized that the connectivity in resting-state networks would be altered, and that the strength of connectivity in areas rich in target receptors would be particularly affected. Additionally, based on known anxiolytic mechanisms of benzodiazepines, modulated amygdala (Am) connectivity was predicted. To test this, seed region-based correlational analysis was performed using seven seeds placed in well-characterized resting-state networks, in regions with above-average densities of GABA-A or dopamine receptors and in Am. To alleviate the anatomical bias introduced by the a priori selected seed regions, whole-brain exploratory analysis of regional homogeneity and fractional amplitude of low-frequency fluctuations (fALFF) was also carried out. Oxazepam increased functional connectivity between midline regions of the default-mode network (DMN) and the prefrontal, parietal, and cerebellar areas, but decreased connectivity between, for example, the Am and temporal cortex. L-dopa mainly decreased connectivity between the Am and bilateral inferior frontal gyri and between midline regions of the DMN. The fALFF analysis revealed that L-dopa decreased low-frequency fluctuations in the cerebellum. It was concluded that the overall effects of single administrations of oxazepam and L-dopa on resting-state connectivity were small both in strength and in spatial extent, and were on par with placebo effects as revealed by comparing the two placebo groups.

In the present study we describe the synthesis, wet spinning, mechanical testing, and degradation of poly(urethane urea)s (PUURs) intended for clinical use in anterior cruciate ligament (ACL) reconstruction. The effects of soft segment chemical composition and molar mass and the kind of diamine chain extender on the material properties were investigated. It was found that the fibers made of PUUR with polycaprolactone diol (PCL530) as soft segment and MDI/1,3-DAP as hard segment (PCL530-3) have high tensile strength and high modulus and when degraded keep their tensile strength for the time demanded for the application. In conclusion, from a chemical and mechanical point of view PUUR fibers of PCL530-3, ARTELON, are suitable for designing a degradable ACL device.

The present report describes the mechanical tests, in vitro and in vivo studies of a poly(urethane urea) (PUUR) intended for clinical use in anterior cruciate ligament (ACL) reconstruction. In the mechanical tests, no evidence of severe fatigue was observed after repeated cyclic loading. Testings for mutagenicity and delayed contact hypersensitivity were found negative. Three in vivo studies were performed in rabbits and minipigs. Altogether 35 rabbits were operated upon in (1) an intraarticular implantation study, performed to evaluate the soft tissue response to woven bands and fiber bundles of PUUR and (2) a rabbit ACL study, examining the function of the PUUR ACL replacement and the tissue response to the material. In a third study, PUUR ACL replacement in minipigs was evaluated. Taken together, ingrowth of connective tissue in close contact with the PUUR fibers was detected both in rabbits and minipigs. The first clear histological signs of degradation of the polymer was detected after 24 months. In conclusion, the evaluated mechanical properties of the PUUR band correspond to those of the mature, human ACL. Furthermore, both from a histological and functional point of view, the PUUR woven band show interesting properties for future clinical ACL reconstructions.

Glucocorticosteroid, methylprednisolone sodium succinate (MPSS), 30 mg/kg of body weight, or dexamethasone sodium phosphate (DSP), 6 mg/kg of body weight, were given intravenously to 60 patients, divided into two groups of 30 45 minutes prior to cardiopulmonary bypass for coronary artery bypass. These two groups were compared with 30 patients in a control group receiving a placebo and undergoing the same surgery. The study was carried out in a double-lind fashion. Patients receiving MPSS had a significantly higher cardiac index in both the preoperative and postoperative periods. This was accompanied by a decreased peripheral resistance. Patients receiving either MPSS or DSP also showed some evidence for the "washout" phenomenon indicating the possibility of better microcirculatory flow. Gluconeogenesis may have been enhanced in both groups receiving MPSS or DSP, but the evidence was greater in thos patients receiving MPSS. There were no hospital deaths in any of the three groups totaling 90 patients.