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Background Evidence for the effects of exercise and dietary interventions on cognition from long-term randomized controlled trials (RCTs) in large general populations remains insufficient. Objective The objective of our study was to investigate the independent and combined effects of resistance and aerobic exercise and dietary interventions on cognition in a population sample of middle-aged and older individuals. Methods We conducted a 4-y RCT in 1401 men and women aged 57-78 y at baseline. The participants were randomly assigned to the resistance exercise, aerobic exercise, diet, combined resistance exercise and diet, combined aerobic exercise and diet, or control group. Exercise goals were at least moderate-intensity resistance exercise ≥2 times/wk and at least moderate-intensity aerobic exercise ≥5 times/wk. Dietary goals were ≥400 g/d of vegetables, fruit, and berries; ≥2 servings of fish/wk; ≥14 g fiber/1000 kcal; and ≤10% of energy of daily energy intake from SFAs. The primary outcome was the change in global cognition measured by the total score of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological tests [CERAD total score (CERAD-TS)]. The data were analyzed using the intention-to-treat principle and linear mixed-effects models. Results There was a trend toward improved CERAD-TS over 4 y in the combined aerobic exercise and diet group compared with the control group (net increase: 1.4 points; 95% CI: 0.1, 2.7; P = 0.06) adjusted for age, sex, years of education, symptoms of depression, and waist circumference at baseline. No other differences in CERAD-TS changes were found across the 6 study groups. Diet did not potentiate the effect of aerobic or resistance exercise on CERAD-TS. Conclusions A combination of at least moderate-intensity aerobic exercise and a healthy diet may improve cognition in older individuals over 4 y, but there was no effect of either of these interventions alone, resistance training alone, or resistance exercise with a healthy diet on cognition.

Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer’s disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.

Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n = 102) and patients with epilepsy (n = 33) and furthermore to drug-naive seizure patients (n = 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11–0.51 Hz) were significantly (P, The study reports markedly elevated focal respiratory-related brain pulsation in epilepsy. The novel technique based on fast functional MRI enables non-invasive evaluation of both individual- and group-level changes. Presented findings suggest a link between epilepsy and glymphatic pulsation abnormality., Graphical Abstract Graphical Abstract

Background Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods The participants (N = 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes (SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility. The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from the Brainmap database). Results At the global level, participants with psychotic-like symptoms had higher CVBOLD in cerebrospinal fluid (CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analyses revealed that CVBOLD was increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlapped Background: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods: The participants (N= 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes(SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility.The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from theBrainmap database). Results: At the global level, participants with psychotic-like symptoms had higher CVBOLDin cerebrospinal fluid(CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analy-ses revealed that CVBOLDwas increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlappedb6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. Conclusions: Psychotic-like symptoms were associated with elevated CVBOLDin a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.

This study investigated whole-brain dynamic lag pattern variations between neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) by applying a novel technique called dynamic lag analysis (DLA). The use of 3D magnetic resonance encephalography data with repetition time = 100 msec enables highly accurate analysis of the spread of activity between brain networks. Sixteen resting-state networks (RSNs) with the highest spatial correlation between NT individuals (n = 20) and individuals with ASD (n = 20) were analyzed. The dynamic lag pattern variation between each RSN pair was investigated using DLA, which measures time lag variation between each RSN pair combination and statistically defines how these lag patterns are altered between ASD and NT groups. DLA analyses indicated that 10.8% of the 120 RSN pairs had statistically significant (P-value

Previously, schizophrenia is found to be related to the variability of the functional magnetic resonance imaging (fMRI) signal in the white matter. However, evidence about the relationship between genetic vulnerabilities and physiological fluctuation in the brain is lacking. We investigated whether familial risk for psychosis (FR) and polygenic risk score for schizophrenia (PRS) are linked with physiological fluctuation in fMRI data. We used data from the Oulu Brain and Mind study (n. = 140-149, aged 20-24 years) that is a substudy of the Northern Finland Birth Cohort 1986. The participants underwent a resting-state fMRI scan. Coefficient of variation (CV) of blood oxygen level dependent (BOLD) signal (CVBOLD) was used as a proxy of physiological fluctuation in the brain. Familial risk was defined to be present if at least one parent had been diagnosed with psychosis previously. PRS was computed based on the results of the prior GWAS by the Schizophrenia Working Group. FR or PRS were not associated with CVBOLD in cerebrospinal fluid, white matter, or grey matter. The findings did not provide evidence for the previous suggestions that genetic vulnerabilities for schizophrenia become apparent in alterations of the variation of the BOLD signal in the brain.

The symptoms of ADHD tend to have continuity to adulthood even though the diagnostic criteria were no longer fulfilled. The aim of our study was to find out possible differences in BOLD signal in the face-processing network between adults with previous ADHD (pADHD, n = 23) and controls (n = 29) from the same birth cohort when viewing dynamic facial expressions. The brain imaging was performed using a General Electric Signa 1.5 Tesla HDX. Dynamic facial expression stimuli included happy and fearful expressions. The pADHD group demonstrated elevated activity in the left parietal area during fearful facial expression. The Network Based Statistics including multiple areas demonstrated higher functional connectivity in attention related network during visual exposure to happy faces in the pADHD group. Conclusions: We found differences in brain responses to facial emotional expressions in individuals with previous ADHD compared to control group in a number of brain regions including areas linked to processing of facial emotional expressions and attention. This might indicate that although these individuals no longer fulfill the ADHD diagnosis, they exhibit overactive network properties affecting facial processing.

Objective The cerebellum plays a critical role in cognition and behavior. Altered function of the cerebellum has been related to schizophrenia and psychosis but it is not known how this applies to spontaneous resting state activity in young people with familial risk for psychosis. Methods We conducted resting-state functional MRI (R-fMRI) in 72 (29 male) young adults with a history of psychosis in one or both parents (FR) but without their own psychosis, and 72 (29 male) similarly healthy control subjects without parental psychosis. Both groups in the Oulu Brain and Mind Study were drawn from the Northern Finland Birth Cohort 1986. Participants were 20–25 years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data pre-processing was conducted using independent component analysis with 30 and 70 components. A dual regression technique was used to detect between-group differences in the cerebellum with p Results FR participants demonstrated statistically significantly increased activity compared to control subjects in the anterior lobe of the right cerebellum in the analysis with 70 components. The volume of the increased activity was 73 mm 3 . There was no difference between the groups in the analysis with 30 components. Conclusion The finding suggests that increased activity of the anterior lobe of the right cerebellum may be associated with increased vulnerability to psychosis. The finding is novel, and needs replication to be confirmed.

According to the disconnectivity model, disruptions in neural connectivity play an essential role in the pathology of schizophrenia. The aim of this study was to determine whether these abnormalities are present in young adults with familial risk (FR) for psychosis in the general population based sample. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to compare whole-brain fractional anisotropy, mean diffusivity, and axial and radial diffusion in 47 (17 males) FR subjects to 51 controls (17 males). All the participants were aged between 20 and 25 years and were members of the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind Study). Region of interest analyses were conducted for 12 tracts. Separately, we analysed whole-brain FA for the subgroup with FR for schizophrenia (n=13) compared with 13 gender-matched controls. Contrary to our expectations there were no differences in any of the DTI measures between FR and control groups. This suggests that white matter abnormalities may not be a genetic feature for risk of psychosis and preceding the onset of a psychotic disorder. Our findings do not support the theory of disconnectivity as a primary sign of psychosis in young adults with FR for the illness.

Purpose The aim of this research was to examine the association between statin use and the risk of acute pancreatitis. Methods This register-based case–control study with incidence density sampling was based on 4376 patients hospitalized in 2008–2010 for acute pancreatitis and 19 859 randomly selected age and sex-matched controls from the adult population of Finland. The relationship between statin use from 1 January 2004 to the index date and the relative incidence rate of acute pancreatitis was modelled by conditional logistic regression. The rate ratios were adjusted for comorbidities. Results A total of 826 (19%) cases and 2589 (13%) controls had been exposed to statins. Statin use was associated with an increased incidence rate of acute pancreatitis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.13–1.39). This increase was seen especially during the first year of use both among current (OR 1.37, 95% CI 0.94–2.00 for at most 3 months of use and OR 1.32, 95% CI 1.07–1.63 for 4–12 months of use) and former users (OR 1.64, 95% CI 1.33–2.03). The overall association remained when restricting analyses to participants with current use only, or with no history of gallstone or alcohol-related diseases, or with no comorbidities or medicines other than statins. Conclusions Statin use seems to be associated with an increased risk of acute pancreatitis. The association is more apparent during the first year of statin use and among former users. Copyright © 2015 John Wiley & Sons, Ltd.

[EN] The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder., This work was supported by grants from the Academy of Finland (grant numbers 132 071, 278 286, 268 336), the Sigrid Juselius Foundation, the Brain & Behavior Research Foundation, the Orion Research Foundation sr, the Foundation for Psychiatric Research, The scholarship Fund of the University of Oulu -Tyyni Tani Found, the University of Oulu Scholarship Foundation, the Jalmari and Rauha Ahokas Foundation, The Maud Kuistila Memorial Foundation, the Jane and Aatos Erkko Foundation, and the Oy H Lundbeck Ab. The funders had no role in the study design, data collection, data analysis, interpreting the results or the decision to publish the article.

Article, High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning., final draft, http://purl.org/eprint/status/PeerReviewed

Objective: To describe the association between teachers’ beliefs about medicines and teaching about illnesses and medicines-related topics by Finnish comprehensive school teachers. Design: A nationwide postal survey. Setting: Finnish primary and lower secondary school teachers. Method: Data were collected using a nationwide postal survey from a representative sample ( n = 1700) of Finnish primary and lower secondary school teachers in spring 2010. A response rate of 56% ( n = 928) was achieved, from which 667 teachers had taught health-related topics. Logistic regression multivariate analysis was used to measure key associations. Results: Among primary school teachers, stronger beliefs about the harmfulness of medicines were associated with teaching basic knowledge about what medicines are (odds ratio [OR] 1.86, 95% confidence interval [CI] = 1.01–3.45). Although an association was detected, other explanatory factors, for example, teachers’ experience of medicating a long-term illness in their own child, their teaching experience and a qualification in health education and perceived teaching skills, seemed to predict the teaching more than teachers’ beliefs about medicines. Conclusion: Findings have important implications for teacher training and continuing education. If teachers can become more aware of the beneficial aspects of teaching about the rational use of medicines, this may lead to greater inclusion of medicines-related education in school health education.

Aims To assess the efficacy of methylphenidate as a substitution therapy for amphetamine/methamphetamine dependence in Finland and New Zealand. Design Parallel-group, double-blind, randomized placebo-controlled trial. Setting Out-patient care. Participants Amphetamine-/methamphetamine-dependent, aged 16–65 years. Measurements The primary outcome measure was presence/absence of amphetamine/methamphetamine in urine samples collected twice weekly. Secondary measures included treatment adherence, alterations in craving scores and self-reported use. Primary analysis was by intention-to-treat (ITT). The study drug, methylphenidate (as Concerta®), was up-titrated over 2 weeks to a maximum dose of 54 mg daily and continued for a further 20 weeks. Doses were given under daily supervision at the clinics. Findings Seventy-nine participants were randomized (40 methylphenidate; 39 placebo); 76 received allocated treatment and 27 completed the trial. ITT analysis (n = 78) showed no statistically significant difference in the percentage of positive urines between the methylphenidate and placebo arms (odds ratio: 0.95, 95% confidence interval: 0.83–1.08). However, there was a significant difference (P

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD.

Aim: Set within the general population-based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first-degree relative with psychotic illness or due to having experienced psychotic-like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview. Methods: Prospectively collected data from earlier follow-ups of this cohort were combined with health register data to categorize subjects as those with familial risk (n = 272), symptomatic risk (n = 117), psychosis (n = 78), attention deficit hyperactivity disorder (ADHD) (n = 103) and a sample of controls (n = 193) drawn randomly from the remaining cohort. The Structured Interview for Prodromal Syndromes (SIPS) was applied to all, 295 participants together with questionnaires measuring psychosis vulnerability and schizotypal traits. Results: There were 29 (10%) current prodromal cases. Criteria for the current prodromal syndrome were fulfilled by 12% of the familial risk group and 19% of the symptomatic risk group, compared with 5% of the ADHD group and 4% of controls. Conclusion: We successfully detected young people with a prodromal psychosis syndrome although relatively few subjects deemed to be at high risk met the full operational criteria according to the SIPS interview. Combining methods from familial, clinical and psychometric high-risk approaches provides a tractable method for studying risk of psychosis in the general population.

Background— Previous studies indicate that increased QRS duration in ECG is related to the risk of all-cause death. However, the association of QRS duration with the risk of sudden cardiac death (SCD) is not well documented in large population-based studies. Our aim was to examine the relation of QRS duration with SCD in a population-based sample of men. Methods and Results— This prospective study was based on a cohort of 2049 men aged 42 to 60 years at baseline with a 19-year follow-up, during which a total of 156 SCDs occurred. As a continuous variable, each 10-ms increase in QRS duration was associated with a 27% higher risk for SCD (relative risk, 1.27; 95% confidence interval, 1.14–1.40; P 110 ms (highest quintile) had a 2.50-fold risk for SCD (relative risk, 2.50; 95% confidence interval, 1.38–4.55; P =0.002) compared with those with QRS duration of Conclusions— QRS duration is an independent predictor of the risk of SCD and may have utility in estimating SCD risk in the general population.

Objectives In tinnitus rTMS treatment, the inhibitory 1 Hz stimulation is commonly delivered to left auditory cortex and/or left temporoparietal junction (TPJ). We aimed to improve rTMS-targeting with fMRI measurements. Methods A patient with whiplash and head trauma originated brain injury leading to constant headache, bilateral tinnitus and hearing deficit, and depression. Tinnitus handicap index (0–100) (THI) was 74 before therapy. The patient received two 4-week rTMS therapy series. Primary treatment side was left based on literature and MRI perfusion images. Targets were on primary auditory cortex bilaterally and on left TPJ. Several adjustments to target locations were tested in chasing of the positive patient feedback. Inhibitory TMS-parameters for each target were 1 Hz and 1000–1500 pulses. Before and after treatment series resting-state fMRI was acquired and a local synchrony measure (ReHo) was computed. Results After the first treatment series the left side tinnitus was relieved (THI dropped from 74 to 22) but right side tinnitus remained and later THI got back to 74. After three months, patient received the second series and left side tinnitus was again attenuated, but right side tinnitus remained. Then fMRI ReHo analysis was re-checked and a hypersyncronous right posterior temporal cortex spot was noticed. Using that as an rTMS-target led to a quick attenuation of the remaining right side tinnitus. THI dropped to 12 and the treatment effect has persisted. Conclusions fMRI informed personalized rTMS-treatment has the potential to target the correct gyrus and hemisphere without extensive trial and error, at least in tinnitus.

Cardiorespiratory fitness is currently estimated by dividing maximal oxygen consumption (VO(2max)) by body weight (per-weight standard). However, the statistically correct way to neutralize the effect of weight on VO(2max) in a given population is adjustment for body weight by regression techniques (adjusted standard). Our objective is to quantify the bias introduced by the per-weight standard in a population distributed across different categories of body mass.This is a cross-sectional study.Baseline measures from participants of the Dose-Responses to Exercise Training Study (DR's EXTRA), 635 men (body mass index (BMI): 19-47 kg m⁻²) and 638 women (BMI: 16-49 kg m⁻²) aged 57-78 years who performed oral glucose tolerance tests and maximal exercise stress tests with direct measurement of VO(2max). We compare the increase in VO(2max) implied by the per-weight standard with the real increase of VO(2max) per kg body weight. A linear logistic regression model estimates odds for abnormal glucose metabolism (either impaired fasting glycemia or impaired glucose tolerance or Type 2 diabetes) of the least-fit versus most-fit quartile according to both per-weight standard and adjusted standard.The per-weight standard implies an increase of VO(2max) with 20.9 ml min⁻¹ in women and 26.4 ml min⁻¹ in men per additional kg body weight. The true increase per kg is only 7.0 ml min⁻¹ (95% confidence interval: 5.3-8.8) and 8.0 ml min⁻¹ (95% confidence interval: 5.3-10.7), respectively. Risk for abnormal glucose metabolism in the least-fit quartile of the population is overestimated by 52% if the per-weight standard is used.In comparisons across different categories of body mass, the per-weight standard systematically underestimates cardiorespiratory fitness in obese subjects. Use of the per-weight standard markedly inflates associations between poor fitness and co-morbidities of obesity.

To investigate whether levosimendan diminishes the incidence of heart failure after cardiac surgery.Prospective, randomized, placebo-controlled clinical study.Cardiac surgery operating room and postanesthesia care unit in a university hospital.Two hundred patients assigned to undergo heart valve or combined heart valve and coronary artery bypass grafting surgery.Patients were randomized to receive a 24-hr infusion of placebo or levosimendan administered as a 24 μg/kg bolus over 30-mins and thereafter at a dose of 0.2 μg/kg/min.Heart failure was defined as cardiac index2.0 L/min/m or failure to wean from cardiopulmonary bypass necessitating inotrope administration for at least 2 hrs postoperatively. Heart failure was less frequent in the levosimendan compared to the placebo group: 15 patients (15%) in the levosimendan and 59 patients (58%) in the placebo group experienced heart failure postoperatively (risk ratio 0.26; 95% confidence interval 0.16-0.43; p.001). Accordingly, a rescue inotrope (adrenaline) was needed less frequently in the levosimendan compared to the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.89), p=.005. Intra-aortic balloon pump was utilized in one patient (1%) in the levosimendan and in nine patients (9%) in the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.87), p=.018. The hospital and the 6-month mortality were comparable between groups. There were no significant differences in major organ failures postoperatively. Eighty-three patients were hypotensive and needed noradrenaline in the levosimendan compared to 52 patients in the placebo group, p.001. The cardiac enzymes (creatine kinase MB isoenzyme mass) indicating myocardial damage were lower in the levosimendan group on the first postoperative day, p=.011.In the present study, levosimendan infusion reduced the incidence of heart failure in cardiac surgery patients but was associated with arterial hypotension and increased requirement of vasopressor agents postoperatively. Improved mortality or morbidity was not demonstrated.

Savonen KP, Kiviniemi V, Laaksonen DE, Lakka TA, Laukkanen JA, Tuomainen T-P, Rauramaa R (Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Kuopio University Hospital, Kuopio; Information Technology Center, University of Eastern Finland, Kuopio Campus, Kuopio; Kuopio University Hospital, Kuopio; Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus; and Lapland Central Hospital, Rovaniemi, Finland). Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men. J Intern Med 2011; doi: 10.1111/j.1365-2796.2011.02434.x Background. A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables. Methods. The study subjects were a representative population-based sample of 1102 men (42–61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models. Results. During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min−1, relative risk (RR) 1.16, 95% CI 1.02–1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min−1, RR 1.09, 95% CI 0.93–1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min−1, RR 1.12, 95% CI 0.98–1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker. Conclusion. A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity.

FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD in multiple regions. Negative valence increased deactivation in visual areas in subjects with ASDs. The most marked differences between valences focus on fronto-insular and temporal regions. This supports the idea that subjects with ASDs may have difficulty in passive processing of the salience and mirroring of expressions. When the valence scaling of brain activity fails, in contrast to controls, these areas activate and/or deactivate inappropriately during facial stimuli presented dynamically.

BACKGROUND: The incidence of nasolacrimal pathway obstruction increases with age, and dacryocystorhinostomy (DCR) is a commonly applied surgical technique to treat severe cases. However, no disease-specific tools to assess the symptoms and the subjective outcome after DCR have been established. We have developed a specific Nasolacrimal Duct Obstruction Symptom Score (NLDO-SS) questionnaire to evaluate the outcome, and tested it in a prospective clinical trial. STUDY DESIGN: Prospective clinical follow-up study. METHODS: Sixty-eight consecutive primary endoscopic dacryocystorhinostomy (EN-DCR) procedures were performed in 64 patients during 2004-2008. Preoperatively and during the three follow-up visits (at 1 week, 2 and 6 months), the patients filled in the NLDO-SS, and at the second and third follow-up visits they also filled in the Glasgow Benefit Inventory (GBI) questionnaire. At one year after the operation, a GBI questionnaire was sent to the patients. RESULTS: The surgical success rate of EN-DCR was 93 %. EN-DCR resulted in a significant reduction in all of the eight symptoms scores of the NLDO-SS (p= 0.001). The GBI scores indicated a significant benefit at 2 months (+37 (SD; 28) and an even higher benefit at 6 months after surgery (+52 (SD; 29), p= 0.001), but no further improvement was found between 6 and 12 months (+52 vs +52, p= 1.0). The correlation between the total GBI and NLDO-SS was significant (p=0.001). CONCLUSIONS: EN-DCR significantly improves the quality of life as measured by the GBI. The NLDO-SS correlated with the GBI and gave more information about the benefits after EN-DCR than GBI alone. The NLDO-SS proved to be an effective tool to evaluate lacrimal obstructions and EN-DCR benefits. Further studies to validate NLDO-SS are needed.

Background Observational studies suggest that higher levels of physical activity and cardiorespiratory fitness associate with improved cognition. However, evidence from randomised controlled trials (RCT) is limited. We hypothesised that increased regular exercise improves cognition in older individuals. The trial is registered: ISRCTN45977199 (http://isrctn.org). Methods A population sample of 1335 men and women aged 57–78 years was randomised into aerobic exercise, resistance exercise, diet, combined aerobic exercise and diet, combined resistance exercise and diet or reference group for a 4-year intervention. Here, we report 2-year interim data. Exercise was assessed by a questionnaire and by maximal oxygen uptake (VO 2max ), an objective measure of exercise, and cognition using Consortium to establish a registry for Alzheimer's disease (CERAD) neuropsychological tests. Findings In the intention to treat analyses, regular exercise increased in exercise groups, but remained unchanged in reference and diet only groups ( P 2max remained unchanged in exercise groups, but decreased in reference and diet only groups ( P 2max to cognition during the first 2 years of intervention. In secondary analyses, improved VO 2max was associated with improved immediate memory in aerobic (β=0.11, P =0.001), resistance (β=0.08, P =0.018), diet (β=0.09, P =0.029) and combined aerobic and diet groups (β=0.09, P =0.013), with improved delayed memory in diet group (β=0.08, P =0.015) and with verbal performance in aerobic group (β=0.14, P =0.044). Those who were in the upper gender-specific VO 2max tertile had a 66.0% (95% confidence interval [CI] 34.2–82.4%, P =0.001) lower, and those in the middle tertile a 56.4% (95% CI 22.6–75.4%, P =0.005) lower risk of developing impaired delayed memory compared to those in the lower VO 2max tertile, after adjusting for potential confounders. Conclusions Present data from a large RCT among older individuals failed to show between group differences on the effects of regular exercise on cognition. However, secondary analyses suggest that higher levels of fitness may potentially mitigate memory impairment.

Objectives Our aim was to examine the relation of cardiorespiratory fitness with sudden cardiac death (SCD) in a population-based sample of men. Background Very limited information is available about the role of cardiorespiratory fitness in the prediction of SCD. Methods This population study was based on 2,368 men 42 to 60 years of age. Cardiorespiratory fitness was defined by using respiratory gas exchange analyzer and maximal workload during cycle ergometer exercise test. Results During the 17-year follow-up, there were 146 SCDs. As a continuous variable, 1 metabolic equivalent (MET) increment in cardiorespiratory fitness was related to a decrease of 22% in the risk of SCD (relative risk: 0.78, 95% confidence interval: 0.71 to 0.84, p Conclusions Cardiorespiratory fitness is a predictor of SCD in addition to that predicted by conventional risk factors. There was a slight improvement in the level of discrimination, although the net reclassification index did not change while using cardiorespiratory fitness with conventional risk factors.

To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers.Prospective, partly randomized trial.Kuopio University Hospital, Finland.167 osteoporotic women (61+/-2.7 years; T-scoreor=-2.5 SD).Estradiol 2 mg+NETA 1 mg, randomization to additional 800 mg clodronate (n=55, HT+C-group) or placebo (n=55, HT-group); if contraindications to HRT, clodronate (n=57, C-group).BMD by DXA after 1, 3 and 5 years, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) at the baseline and after 3 years.After 5 years, adjusted lumbar BMD increased by 4.2% in the HT-group and 3.7% in the HT+C-group. The C-group showed a decrease of -1.1%, the total difference being 5.3% and 4.8% between HT, HT+C vs. C-group, respectively (p0.001). In the femoral neck, the adjusted 5-year BMD benefit was 1.3% and 2.4% in the HT- and HT+C-groups, respectively, the net loss of BMD in the C-group was -3.3% (p0.05 between HT+C vs. C). By 3 years, OC decreased by 55.0%, 70.3% and 53.8% in the HT-, HT+C- and C-groups, respectively (p0.001 vs. baseline). The significant decreases of BAP were 39.4% in the HT-group, 42.1% in the HT+C-group and 30.2% in the C-group with no significant differences between the groups after adjustments.In postmenopausal women with osteoporosis, HRT increased spinal and femoral BMD, but the combination of HRT and clodronate did not offer an extra gain of bone mass.

This paper assessed the neural systems involved in processing of dynamic facial expressions in adolescents. The processing of facial expressions changes as a function of age, and it is thus important to understand how healthy adolescent subjects process dynamic facial expressions prior to analyzing disease-related changes. We hypothesized that viewing of dynamic facial expressions with opposing valences (happy vs. fearful) induces differential activations and deactivations in the brain. 27 healthy adolescents (9 female, 18 male, mean age = 14.5 years; age range 11.6-17.3 years) were examined by using the ASSQ and K-SADS-PL and scanned with 1.5-T fMRI during viewing of dynamic facial expressions and mosaic control images. The stimuli activated the same areas as previously seen in dynamic facial expression in adults. Our results indicated that opposing-valence dynamic facial expressions had differential effects on many cortical structures but not on subcortical limbic structures. The mirror neuron system is activated more during viewing of fearful compared to happy expressions in bilateral inferior frontal gyrus (IFG) and superior temporal sulcus (STS) left dominantly. We also detected more deactivation in the ventral anterior cingulate gyrus (ACG), showing more automated attentional processing of fearful expressions during passive viewing. Females were found to deactivate the right frontal pole more than male adolescents during happy facial expressions, while there were no differences in fear processing between genders. No clear gender or age effects were detected. In conclusion fear induces stronger responses in attention and mirror neurons probably related to fear contagion.

Aim The aim of the present study was to assess the relationship between patient-to-registered nurse (RN) ratios and nursing outcomes: job satisfaction and stress, nursing care quality, control of own practise, intent to leave, adequacy of material resources and attitudes towards technical equipment. Background Although there is a growing body of evidence showing that higher levels of RN staffing are linked to better outcomes, it still is unclear how nurse staffing produces these effects. Method A survey of data of RNs (n = 854) in 46 inpatient units at five university hospitals in Finland was used to create a Bayesian network (BN) model of connections between the variables. Results A BN model constructed showed that the quality of nursing care is influenced by multifaceted work environment measures. RNs’ possibility to control their own practice and the quality of care are mediation between patient-to-RN ratio and other variables examined. Conclusions New insight was given to the complex theme of the nursing practice environment and its connections to nursing outcomes. Implications for nursing management Work environment should be developed with consideration of many factors, including adequate staffing levels and the ability for nurses to control their own work. This could increase nurses’ work satisfaction, retention and patient care quality outcomes.

Background: In general, in-hospital resuscitation is performed in a bed and out-of-hospital resuscitation on the floor. The surface under the patient may affect the cardiopulmonary resuscitation (CPR) quality; therefore, we evaluated CPR quality (the percentage of chest compressions of correct depth) and rescuer's fatigue (the mean compression depth minute by minute) when CPR is performed on a manikin on the floor or in the bed. Methods: Forty-four simulated cardiac arrest scenarios of 10 min were treated by intensive care unit (ICU) nurses in pairs using a 30 : 2 chest compression-to-ventilation ratio. The rescuer who performed the compressions was changed every 2 min. CPR was randomly performed either on the floor or in the bed without a backboard; in both settings, participants kneeled beside the manikin. Results: A total number of 1060 chest compressions, 44% with correct depth, were performed on the floor; 1068 chest compressions were performed in the bed, and 58% of these were the correct depth. These differences were not significant between groups. The mean compression depth during the scenario was 44.9±6.2 mm (mean±SD) on the floor and 43.0±5.9 mm in the bed (P=0.3). The mean chest compression depth decreased over time on both surfaces (P

Clozapine is the drug of choice for patients with unsatisfactory response to routine antipsychotic treatment. Polypharmacy is widely used among patients having clozapine-resistant schizophrenia, although no solid evidence exists for any effective augmentation therapy for this patient population. We aimed to study the efficacy of lamotrigine in the treatment of clozapine-resistant schizophrenia.We conducted electronic searches of the Cochrane PsiTri database, the Website of metaRegister of Controlled Trials, including NIH ClinicalTrials.gov, and a clinical trial register by the manufacturer of lamotrigine (GlaxoSmithKline). All randomized placebo-controlled studies on patients receiving clozapine were included in the analysis. The primary outcome measure was a total score for symptoms of psychosis, and the secondary outcome measures were scores for positive and negative symptoms of psychosis. For continuous and binary data, standardized mean differences (SMD), and odds ratios (OR) and the number needed to treat (NNT) were calculated, respectively.Five trials with 10 to 24 weeks duration and total of 161 randomized clozapine patients were included in the meta-analysis. Lamotrigine was superior to placebo augmentation in both the primary outcome measure (SMD 0.57, 95%CI 0.25-0.89, p0.001; OR 0.19, 95%CI 0.09-0.43, p0.001; NNT 4, 95%CI 3-6) and secondary outcome measures (SMD 0.34, 95%CI 0.02-0.65 for positive symptoms, SMD 0.43, 95%CI 0.11-0.75 for negative symptoms).This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia. A substantial proportion of these most severely ill patients appeared to obtain clinically meaningful benefit from this combination treatment.

To compare 14-gauge SCNB (stereotactic core needle biopsy) with surgery and to investigate tissue-heterogeneity of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth-factor receptor (HER-2) for nonpalpable breast cancers. To determine the number of cores needed for assessment of these factors.Cores of 41 invasive cancers were collected in three containers: the 1st into A, the 2nd and 3rd into B and subsequent cores into C. ER, PR and HER-2 were scored by immunohistochemistry and if 2+ or 3+, by chromogenic-in-situ-hybridisation (CISH) for containers and for surgical specimen.Between SCNB and surgical specimen concordance was 83% (kappa = 0.39) for ER, 88% (kappa = 0.69) for PR and HER-2 and 93% (kappa = 0.63) for HER-2 after CISH. For the most discordant cases, status was positive in cores but negative in surgery: 5/7 for ER (p = 0.459), 5/5 for PR (p = 0.063), and 4/5 for HER-2 (p = 0.375), after CISH 3/3 (p = 0.250), but the difference was not statistically significant. Concordances between containers of cores was 100% (kappa = 1), 85% (kappa = 0.66) and 85% (kappa = 0.66), respectively. With more than three cores, sensitivities of 95%, 100% and 100% were reached.SCNB is at least as sensitive as surgery in assessment of ER, PR and HER-2. Three cores are needed for reliable assessment of HER-2 after adding CISH and more than three cores for PR, possibly due to tissue heterogeneity. For ER sensitivity remained lower, 95%, even in multiple cores, therefore ER-negative cases should be further investigated from surgical specimens.

Introduction: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). Objective: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. Methods: Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. Results: Only the PC20 values of asthmatic subjects differed statistically significantly from those of the healthy group (P

Plant stanol esters in spreads have demonstrated efficacy in reducing serum cholesterol. The cost-effectiveness of plant stanol esters in the prevention of coronary heart disease, however, has remained unevaluated.A Bayesian modelling approach was applied to synthesize clinical evidence and evaluate the cost-effectiveness (Euro/quality-adjusted life years) of plant stanol esters in spread in the prevention of coronary heart disease based on published FINRISK and 4S risk functions.The regular use of plant stanol esters reduced total serum cholesterol by -0.362 mmol/l [95% credibility interval (CrI) -0.31 to -0.41]. The corresponding placebo-adjusted reduction attributable to stanol esters when combined with statin was -0.385 mmol/l (95% CrI -0.18 to -0.61). The cost-effectiveness estimations were assessed for men and women separately at four different initial ages at which the regular use of stanol esters was assumed to be started. The base case cost per quality-adjusted life years gained by using stanol esters regularly ranged from 7436 to 20,999 Euro in men and from 34,327 to 112,151 Euro in women based on the initial starting age. According to uncertainty analysis, there is over a 90% probability that the use of plant stanol esters is cost-effective for men inclusively and for 60-year-old and older women assuming that decision-makers' maximum willingness to pay per quality-adjusted life year is 50,000 Euro.A recommendation that plant stanol ester-containing spreads be used as a part of daily diet replacing regular spread could be viewed as potentially cost-effective public health policy in the prevention of CHD in all adult men and in older age-groups of women with total serum cholesterol levels of 5 mmol/l or greater.

Many doctors consider wheezing infants and young children who respond to beta-adrenergic agents to be asthmatics, or at least at risk for later asthma. The aim of this study was to compare responses to inhaled albuterol and racemic epinephrine in infancy between children with and without asthma later in childhood. In a crossover study setting, 100 acutely wheezing infants aged less than 24 months were randomized to receive inhalations of either racemic epinephrine and placebo, or albuterol and placebo. Clinical evaluation consisted of measurements of respiratory rate, heart rate, and oxygen saturation, and clinical assessment of the respiratory distress assessment instrument (RDAI) score, consisting of wheezing and chest indrawings. The asthma status of the children was evaluated at three clinical follow-up visits, at 4.0, 7.2, and 12.3 (median) years of age. Responses to bronchodilating agents, when respiratory rates and RDAI scores were used as outcome measures, were not different in future asthmatics compared to nonasthmatics. However, oxygen saturation was significantly higher after albuterol inhalation in children who had asthma at all three visits (92.67% confidence interval (CI), 91.39-93.96) than in those without asthma at these visits (92.52% CI, 91.79-93.25), but lower, correspondingly, after racemic epinephrine (91.97% CI, 90.74-93.19 vs. 93.04% CI, 92.29-93.79) and placebo (91.38% CI, 90.49-92.28 vs. 93.12% CI, 92.60-93.65) inhalations (P = 0.04). In conclusion, we were not able to confirm that future asthmatics respond better than future nonasthmatics to bronchodilating agents during wheezing in infancy. More studies are needed to characterize the subset of infants who benefit from bronchodilating treatment in infancy.

Laboratory rats are generally fed ad libitum, although this method is associated with obesity and an increased frequency of spontaneous tumours. It has been challenging looking for ways to limit feed consumption in group-housed rats without any setbacks to animal welfare and scientific results. The diet board, as a method of dietary restriction, was used in the present study. Diet board feeding allows group housing and should result in enhanced welfare compared with traditional methods of dietary restriction. With respect to animal model robustness and translatability of results it is important that the feeding regime does not affect diurnal rhythmicity of biological parameters. In the present study the effects of diet board feeding on diurnal rhythms of blood glucose, serum ghrelin, faecal immunoglobulin A (IgA) and faecal corticosterone were assessed. The diet board did not alter diurnal rhythms, and adds weight to the use of this method for dietary restriction which should benefit animal health and the validity of scientific results generated from the animals.

ObjectiveThe cerebellum plays a critical role in cognition and behavior. Altered function of the cerebellum has been related to schizophrenia and psychosis but it is not known how this applies to spontaneous resting state activity in young people with familial risk for psychosis.MethodsWe conducted resting-state functional MRI (R-fMRI) in 72 (29 male) young adults with a history of psychosis in one or both parents (FR) but without their own psychosis, and 72 (29 male) similarly healthy control subjects without parental psychosis. Both groups in the Oulu Brain and Mind Study were drawn from the Northern Finland Birth Cohort 1986. Participants were 20–25 years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data pre-processing was conducted using independent component analysis with 30 and 70 components. A dual regression technique was used to detect between- group differences in the cerebellum with p b 0.05 threshold corrected for multiple comparisons.ResultsFR participants demonstrated statistically significantly increased activity compared to control subjects in the anterior lobe of the right cerebellum in the analysis with 70 components. The volume of the increased activity was 73 mm3. There was no difference between the groups in the analysis with 30 components (Fig. 1).ConclusionThe finding suggests that increased activity of the anterior lobe of the right cerebellum may be associated with increased vulnerability to psychosis. The finding is novel, and needs replication to be confirmed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Background Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment. Methods A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups. Results Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins. Conclusions Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.

Background Social interaction requires mirroring to other people's mental state. Psychotic disorders have been connected to social interaction and emotion recognition impairment. We compared the brain activity between young adults with familial risk for psychosis (FR) and matched controls during visual exposure to emotional facial expression. We also investigated the role of the amygdala, the key region for social interaction and emotion recognition. Methods 51 FR and 52 control subjects were drawn from the Northern Finland 1986 Birth Cohort (Oulu Brain and Mind Study). None of the included participants had developed psychosis. The FR group was defined as having a parent with psychotic disorder according to the Finnish Hospital Discharge Register. Participants underwent functional MRI (fMRI) using visual presentation of dynamic happy and fearful facial expressions. FMRI data were processed to produce maps of activation for happy and fearful facial expression, which were then compared between groups. Two spherical regions of interest (ROIs) in the amygdala were set to extract BOLD responses during happy and fearful facial expression. BOLD responses were then compared with subjects' emotion recognition, which was assessed after fMRI. Psychophysiological interaction (PPI) for the left and right amygdala during happy and fearful facial expression was conducted using the amygdala as seed regions. Results FR subjects had increased activity in the left premotor cortex and reduced deactivation of medial prefrontal cortex structures during happy facial expression. There were no between-group differences during fearful facial expression. The FR group also showed a statistically significant linear correlation between mean amygdala BOLD response and facial expression recognition. PPI showed that there was a significant negative interaction between the amygdala and the dorsolateral prefrontal cortex (dlPFC) and superior temporal gyrus in FR subjects. Conclusions Increased activations by positive valence in FR were in brain regions crucial to emotion recognition and social interaction. Increased activation of the premotor cortex may serve as a compensatory mechanism as FR subjects may have to exert more effort on processing the stimuli, as has been found earlier in schizophrenia. Failure to deactivate PFC structures may imply error in the default mode network. Abnormal PFC function in FR was also suggested by PPI, as the dlPFC showed decreased functional connectivity with the amygdala in the FR group. This may indicate that in FR subjects the amygdala have to take a greater role in emotion recognition and social functioning. This inference was supported by our discovery of statistically significant correlations between the amygdala BOLD response and emotion recognition in the FR group but not in controls.

Background Seborrhoeic dermatitis is a chronic inflammatory skin disorder affecting primarily the skin of the scalp, face, chest, and intertriginous areas, causing scaling and redness of the skin. Current treatment options include antifungal, anti-inflammatory, and keratolytic agents, as well as phototherapy. Objectives To assess the effects of topical pharmacological interventions with established anti-inflammatory action for seborrhoeic dermatitis occurring in adolescents and adults. Search methods We searched the following databases up to September 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 9), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We searched five trials databases and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). Selection criteria We included RCTs in adults or adolescents (> 16 years) with diagnosed seborrhoeic dermatitis of the scalp or face, comparing topical anti-inflammatory treatments (steroids, calcineurin inhibitors, and lithium salts) with other treatments. Data collection and analysis Pairs of authors independently assessed eligibility for inclusion, extracted data, and evaluated the risk of bias. We performed meta-analyses if feasible. Main results We included 36 RCTs (2706 participants), of which 31 examined topical steroids; seven, calcineurin inhibitors; and three, lithium salts. The comparative interventions included placebo, azoles, calcipotriol, a non-steroidal anti-inflammatory compound, and zinc, as well as different anti-inflammatory treatments compared against each other. Our outcomes of interest were total clearance of symptoms, erythema, scaling or pruritus scores, and adverse effects. The risk of bias in studies was most frequently classified as unclear, due to unclear reporting of methods. Steroid treatment resulted in total clearance more often than placebo in short-term trials (four weeks or less) (relative risk (RR) 3.76, 95% confidence interval (CI) 1.22 to 11.56, three RCTs, 313 participants) and in one long-term trial (lasting 12 weeks). Steroids were also more effective in reducing erythema, scaling, and pruritus. Adverse effects were similar in both groups. There may be no difference between steroids and calcineurin inhibitors in total clearance in the short-term (RR 1.08, 95% 0.88 to 1.32, two RCTs, 60 participants, low-quality evidence). Steroids and calcineurin inhibitors were found comparable in all other assessed efficacy outcomes as well (five RCTs, 237 participants). Adverse events were less common in the steroid group compared with the calcineurin group in the short-term (RR 0.22, 95% CI 0.05 to 0.89, two RCTs, 60 participants). There were comparable rates of total clearance in the steroid and azole groups (RR 1.11, 95% CI 0.94 to 1.32, eight RCTs, 464 participants, moderate-quality evidence) as well as of adverse effects in the short-term, but less erythema or scaling with steroids. We found mild (class I and II) and strong (class III and IV) steroids comparable in the assessed outcomes, including adverse events. The only exception was total clearance in long-term use, which occurred more often with a mild steroid (RR 0.79, 95% CI 0.63 to 0.98, one RCT, 117 participants, low-quality evidence). In one study, calcineurin inhibitor was more effective than placebo in reducing erythema and scaling, but there were similar rates in total clearance or adverse events for short-term treatment. In another study, calcineurin inhibitor was comparable with azole when erythema, scaling, or adverse effects were measured for longer-term treatment. Lithium was more effective than placebo with regard to total clearance (RR 8.59, 95% CI 2.08 to 35.52, one RCT, 129 participants) with a comparable safety profile. Compared with azole, lithium resulted in total clearance more often (RR 1.79, 95% CI 1.10 to 2.90 in short-term treatment, one RCT, 288 participants, low-quality evidence). Authors' conclusions Topical steroids are an effective treatment for seborrhoeic dermatitis of the face and scalp in adolescents and adults, with no differences between mild and strong steroids in the short-term. There is some evidence of the benefit of topical calcineurin inhibitor or lithium salt treatment. Treatment with azoles seems as effective as steroids concerning short-term total clearance, but in other outcomes, strong steroids were more effective. Calcineurin inhibitor and azole treatment appeared comparable. Lithium salts were more effective than azoles in producing total clearance. Steroids are similarly effective to calcineurin inhibitors but with less adverse effects. Most of the included studies were small and short, lasting four weeks or less. Future trials should be appropriately blinded; include more than 200 to 300 participants; and compare steroids to calcineurin inhibitors or lithium salts, and calcineurin inhibitors to azoles or lithium salts. The follow-up time should be at least one year, and quality of life should be addressed. There is also a need for the development of well-validated outcome measures.

Purpose: A recent study suggests that transcranial brain targeted light treatment via ear canals may have physiological effects on brain function studied by functional magnetic resonance imaging (fMRI) techniques in humans. We tested the hypothesis that bright light treatment could improve psychomotor speed in professional ice hockey players. Methods: Psychomotor speed tests with audio and visual warning signals were administered to a Finnish National Ice Hockey League team before and after 24 days of transcranial bright light or sham treatment. The treatments were given during seasonal darkness in the Oulu region (latitude 65 degrees north) when the strain on the players was also very high (10 matches during 24 days). A daily 12-min dose of bright light or sham (n = 11 for both) treatment was given every morning between 8 and 12 am at home with a transcranial bright light device. Mean reaction time and motor time were analyzed separately for both psychomotor tests. Analysis of variance for repeated measures adjusted for age was performed. Results: Time × group interaction for motor time with a visual warning signal was p = 0.024 after adjustment for age. In Bonferroni post-hoc analysis, motor time with a visual warning signal decreased in the bright light treatment group from 127 ± 43 to 94 ± 26 ms (p = 0.024) but did not change significantly in the sham group 121 ± 23 vs. 110 ± 32 ms (p = 0.308). Reaction time with a visual signal did not change in either group. Reaction or motor time with an audio warning signal did not change in either the treatment or sham group. Conclusion: Psychomotor speed, particularly motor time with a visual warning signal, improves after transcranial bright light treatment in professional ice-hockey players during the competition season in the dark time of the year.

OBJECTIVE The long-term use of statins may be associated with a decreased risk for gallstones and biliary-induced acute pancreatitis (AP). Our aim was to study the relationship of statin use and outcome of AP. METHODS We investigated the records of 461 consecutive patients with AP and 1140 patients with symptomatic gallstones during 2008 to 2010. The use of lipid-lowering drugs, patient's characteristics, and outcome of patients were recorded. All known risk factors for AP and particularly statin use in idiopathic AP were analyzed. RESULTS Statin use was comparable between the patients with AP (22%) and patients with cholelithiasis (24%). The frequencies of surgical treatment, duration of hospital stay, or mortality were not different between the statin users compared with the nonusers. Idiopathic AP was more often associated with the use of statins than alcohol- or gallstone-induced AP (44% vs 30% vs 13%, P < 0.002). The etiology of AP was alcohol in 56% of the patients, gallstones in 28% of the patients, and unknown (idiopathic) or miscellaneous in 16% of the patients. CONCLUSIONS No beneficial effect of statins was observed in mortality or other outcome parameters of patients with AP. Statin use was more frequent in patients with idiopathic AP than in patients with biliary- or alcohol-induced AP.

OBJECTIVE We studied the association of maximum oxygen uptake (Vo2max) with the development and resolution of metabolic syndrome (MetS) for 2 years in older individuals. RESEARCH DESIGN AND METHODS Subjects were a population sample of 1,226 men and women aged 57–78 years. We assessed Vo2max directly by respiratory gas analysis during maximum exercise testing and used dichotomous and continuous variables for MetS. RESULTS One SD increase in baseline Vo2max associated with 44% (95% CI 24–58) decreased risk of developing MetS. Individuals in the highest third of baseline Vo2max were 68% (37–84) less likely to develop MetS than those in the lowest third. One SD increase in Vo2max increased the likelihood to resolve MetS 1.8 (1.2–2.8) times. Individuals in the highest Vo2max third were 3.9 (1.5–9.9) times more likely to resolve MetS than those in the lowest third. CONCLUSIONS Higher levels of cardiorespiratory fitness protect against MetS and may resolve it in older individuals.

We tested the hypothesis that family risk for psychosis (FR) and clinical risk for psychosis (CR) are associated with structural brain abnormalities, with increased deficits in those at both family risk and clinical risk for psychosis (FRCR). The study setting was the Oulu Brain and Mind Study, with subjects drawn from the Northern Finland 1986 Birth Cohort (n = 9479) using register and questionnaire based screening, and interviews using the Structured Interview for Prodromal Symptoms. After this procedure, 172 subjects were included in the study, classified as controls (n = 73) and three risk groups: FR excluding CR (FR, n = 60), CR without FR (CR, n = 26), and individuals at both FR and CR (FRCR, n = 13). T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. In the comparison between FRCR versus controls, we found lower grey matter volume (GMV) in a cluster (1689 voxels at − 4.00, − 72.00, − 18.00 mm) covering both cerebellar hemispheres and the vermis. This cluster was subsequently used as a mask to extract mean GMV in all four groups: FR had a volume intermediate between controls and FRCR. Within FRCR there was an association between cerebellar cluster brain volume and motor function. These findings are consistent with an evolving pattern of cerebellar deficits in psychosis risk with the most pronounced deficits in those at highest risk of psychosis.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Background Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique enabling visualization and measurement of white matter tracts. Attention deficit hyperactivity disorder (ADHD) has been studied with DTI earlier with variable results, yet there is little research on remitted ADHD. Purpose To compare the brain white matter between ADHD drug naïve subjects whose ADHD symptoms have mostly subsided and healthy controls. Material and Methods Tract-based spatial statistics (TBSS) was used to compare 30 subjects with adolescent ADHD with control subjects at the age of 22–23 years. The study population was derived from a population-based Northern Finland Birth Cohort 1986. Fractional anisotropy (FA), mean diffusivity (MD), and measures of diffusion direction (λ1–3) were calculated. Permutation testing was used to test for differences in mean values of FA, MD, and λ1–3 between the groups. The results were corrected for multiple comparisons across the whole white matter skeleton. Results The ADHD group showed increased FA related to decreased radial diffusivity in the left forceps minor ( P Conclusion In a setting with remitted ADHD, the results may represent a compensatory mechanism in the left forceps minor.

Background and Aims: Atrial fibrillation (AF) is the most common arrhythmia after coronary arteryby pass surgery (CABG). Intravenous metoprolol and biatrial pacing have been reported to be effective in AF prophylaxis after cardiac surgery. The purpose of this trial was to compare the efficacy of intravenous metoprolol versus biatrial pacing combined with oral metoprolol in the prevention of AF after CABG. Methods: A single-centre prospective randomized open trial of 165 consecutive patients undergoing their first CABG. Patients were randomized to receive either intravenous metoprolol infusion 1–3 mg per hour or biatrial overdrive pacing and oral metoprolol (50–150mg) daily for 72 hours after CABG starting immediately after the surgery. AAI pacing with a pacing rate of 10 beats/minute above the baseline heart rate was used. Patients had continuous ECG-monitoring. The primaryend point was the first episode of AF. Results: The incidence of postoperative AF in the intravenous metoprolol and biatrial pacing groups did not differ from each other (14% vs. 18% respecively, p = 0.66). There was no difference in the time of AF on set between the groups (28.2 ± 16.2 h vs. 30.1 ± 21.2 h respectively, p = 0.8). Intravenous metoprolol infusion had to be temporarily interrupted for one hour in eleven patients because of hypotension or bradycardia. One case of bleeding from the left atria related to the pacemaker electrode wire was found. Conclusion: We found no difference in the incidence of AF between patients treated with intravenous metoprolol or the combination of biatrial pacing and oral metoprolol.