↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Träfflista för sökning "WFRF:(Åberg N. David) "

Search: WFRF:(Åberg N. David)

Result 1-50 of 85

Sort/group result

Sort by: Hits per page:

Enumeration	Reference	Cover	Find
1.	Åberg, Maria A I, 1972, et al. (author) Cardiovascular fitness in males at age 18 and risk of serious depression in adulthood: Swedish prospective population-based study 2012 In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:5, s. 352-359 Journal article (peer-reviewed)abstract Background Studies suggest a role for cardiovascular fitness in the prevention of affective disorders. Aims To determine whether cardiovascular fitness at age 18 is associated with future risk of serious affective illness. Method Population-based Swedish cohort study of male conscripts (n = 1 117 292) born in 1950-1987 with no history of mental illness who were followed for 3-40 years. Data on cardiovascular fitness at conscription were linked with national hospital registers to calculate future risk of depression (requiring in-patient care) and bipolar disorder. Results In fully adjusted models low cardiovascular fitness was associated with increased risk for serious depression (hazard ratios (HR) = 1.96, 95%, CI 1.71-2.23). No such association could be shown for bipolar disorder (HR = 1.11, 95% CI 0.84-1.47). Conclusions Lower cardiovascular fitness at age 18 was associated with increased risk of serious depression in adulthood. These results strengthen the theory of a cardiovascular contribution to the aetiology of depression.
2.	Åberg, N David, 1970, et al. (author) Association Between Levels of Serum Insulin-like Growth Factor I and Functional Recovery, Mortality, and Recurrent Stroke at a 7-year Follow-up. 2020 In: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. - : Georg Thieme Verlag KG. - 1439-3646. ; 128:5, s. 303-310 Journal article (peer-reviewed)abstract The association of serum insulin-like growth factor I (s-IGF-I) with favorable outcome after ischemic stroke (IS) beyond 2 years is unknown. We investigated whether the levels of s-IGF-I 3 months post-stroke were associated with functional recovery up to 7 years after IS, considering also mortality and recurrent strokes.Patients (N=324; 65% males; mean age, 55 years) with s-IGF-I levels assessed 3 months after the index IS were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The modified Rankin Scale (mRS) was used to evaluate outcomes at 3 months, 2 and 7 years after IS, and recovery was defined as an improvement, no change, or deterioration in the shifts of mRS score. Baseline stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS).The mRS score distributions were better in the above-median s-IGF-I group (>146.7ng/ml). The s-IGF-I level was not associated with recurrent stroke (N=79) or death (N=44), although it correlated with recovery (r=0.12, P=0.035). In the regression analysis, s-IGF-I associated with recovery between 3 months and 7 years (but not between 2 and 7 years). The associations did not withstand adjustment for age and sex. For comparison, the corresponding associations between 3 months and 2 years withstood all adjustments.The association for s-IGF-I with long-term post-stroke recovery persists after 7 years, which is also reflected in the mRS score distributions at all time-points. The effects are however modest, and not driven by mortality or recurrent stroke.
3.	Djekic, Demir, et al. (author) Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke 2022 In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:21 Journal article (peer-reviewed)abstract Background: We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF.Methods and Results: We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m2 to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m2, compared with those with BMI of 18.5 to <20.0 kg/m2. During a median follow-up of ≈6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m2 compared with those with BMI <20 kg/m2 were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively.Conclusions: Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.
4.	Djekic, Demir, et al. (author) Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke 2022 In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:21 Journal article (peer-reviewed)abstract Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3 +/- 0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4 +/- 10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m(2) to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m(2), compared with those with BMI of 18.5 to <20.0 kg/m(2). During a median follow-up of approximate to 6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m(2) compared with those with BMI <20 kg/m(2) were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.
5.	Gadd, Gustaf, et al. (author) A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1. 2024 In: International journal of molecular sciences. - 1661-6596 .- 1422-0067. ; 25:9 Journal article (peer-reviewed)abstract Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
6.	Henriksson, Malin, et al. (author) Corrigendum to "Effects of exercise on symptoms of anxiety in primary care patients: A randomized controlled trial", published online ahead of print as J Affect Disord. 2021 Oct 10;297:26-34. 2022 In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299 Journal article (peer-reviewed)
7.	Henriksson, Malin, et al. (author) Effects of exercise on symptoms of anxiety in primary care patients: A randomized controlled trial. 2022 In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 297, s. 26-34 Journal article (peer-reviewed)abstract There is a need for high-quality research regarding exercise interventions for persons with anxiety disorders. We investigate whether a 12-week exercise intervention, with different intensities, could reduce anxiety symptoms in patients with anxiety disorders.286 patients were recruited from primary care in Sweden. Severity of symptoms was self-assessed using the Beck Anxiety Inventory (BAI) and the Montgomery Åsberg Depression Rating Scale (MADRS-S). Participants were randomly assigned to one of two group exercise programs with cardiorespiratory and resistance training and one control/standard treatment non-exercise group, with 1:1:1 allocation.Patients in both exercise groups showed larger improvements in both anxiety and depressive symptoms compared to the control group. No differences in effect sizes were found between the two groups. To study a clinically relevant improvement, BAI and MADRS-S were dichotomized with the mean change in the control group as reference. In adjusted models the odds ratio for improved symptoms of anxiety after low-intensity training was 3.62 (CI 1.34-9.76) and after moderate/high intensity 4.88 (CI 1.66-14.39), for depressive symptoms 4.96 (CI 1.81-13.6) and 4.36 (CI 1.57-12.08) respectively. There was a significant intensity trend for improvement in anxiety symptoms.The use of self-rating measures which bears the risk of an under- or overestimation of symptoms.A 12-week group exercise program proved effective for patients with anxiety syndromes in primary care. These findings strengthen the view of physical exercise as an effective treatment and could be more frequently made available in clinical practice for persons with anxiety issues.
8.	Hinwood, M., et al. (author) Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries 2022 In: Bmj Open. - : BMJ. - 2044-6055. ; 12:5 Journal article (peer-reviewed)abstract Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.
9.	Johansson, Inger, 1962, et al. (author) Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells. 2008 In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:5, s. 2191-9 Journal article (peer-reviewed)abstract Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
10.	Johansson, Per, 1966, et al. (author) Serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are increased in Alzheimer's disease. 2013 In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:9, s. 1729-37 Journal article (peer-reviewed)abstract Although insulin-like growth factor-I (IGF-I) is of importance for the adult function of the central nervous system (CNS), little is known of the significance of IGF-I in cerebrospinal fluid (CSF) in relation to Alzheimer's disease (AD).
11.	Kuhn, Hans-Georg, 1961, et al. (author) Authors' reply. : (To: Cardiovascular fitness in males at age 18 and risk of serious depression in adulthood: Swedish prospective population-based study) 2013 In: British journal of psychiatry. - : Royal College of Psychiatrists. - 1472-1465 .- 0007-1250. ; 202:4 Journal article (other academic/artistic)
12.	Lindgren, Martin, et al. (author) Cardiorespiratory fitness and muscle strength in late adolescence and long-term risk of early heart failure in Swedish men. 2017 In: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 24:8, s. 876-884 Journal article (peer-reviewed)abstract Aims To investigate the association between cardiorespiratory fitness (CRF) and muscle strength in late adolescence and the long-term risk of heart failure (HF). Methods A cohort was created of Swedish men enrolled in compulsory military service between 1968 and 2005 with measurements for CRF and muscle strength ( n=1,226,623; mean age 18.3 years). They were followed until 31 December 2014 for HF hospitalization as recorded in the Swedish national inpatient registry. Results During the follow-up period (median (interquartile range) 28.4 (22.0-37.0) years), 7656 cases of first HF hospitalization were observed (mean±SD age at diagnosis 50.1±7.9 years). CRF and muscle strength were estimated by maximum capacity cycle ergometer testing and strength exercises (knee extension, elbow flexion and hand grip). Inverse dose-response relationships were found between CRF and muscle strength with HF as a primary or contributory diagnosis with an adjusted hazards ratio (95% confidence interval) of 1.60 (1.44-1.77) for low CRF and 1.45 (1.32-1.58) for low muscle strength categories. The associations of incident HF with CRF and muscle strength persisted, regardless of adjustments for the other potential confounders. The highest risk was observed for HF associated with coronary heart disease, diabetes or hypertension. Conclusions In this longitudinal study of young men, we found inverse and mutually independent associations between CRF and muscle strength with risk of hospitalization for HF. If causal, these results may emphasize the importance of the promotion of CRF and muscle strength in younger populations.
13.	Lindgren, Martin, et al. (author) Cognitive performance in late adolescence and long-term risk of early heart failure in Swedish men. 2018 In: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 20:6, s. 989-97 Journal article (peer-reviewed)abstract Heart failure (HF) incidence appears to increase among younger individuals, raising questions of how risk factors affect the younger population. We investigated the association of cognitive performance in late adolescence with long-term risk of early HF.We followed a cohort of Swedish men enrolled in mandatory military conscription in 1968-2005 (n=1 225 300; mean age 18.3years) until 2014 for HF hospitalization, using data from the Swedish National Inpatient Registry. Cognitive performance (IQ) was measured through a combination of tests, separately evaluating logical, verbal, visuospatial, and technical abilities. The results were standardized, weighted, and presented as stanines of IQ. The association between IQ and risk of HF was estimated using Cox proportional hazards models. In follow-up, there were 7633 cases of a first HF hospitalization (mean age at diagnosis 50.1years). We found an inverse relationship between global IQ and risk of HF hospitalization. Using the highest IQ stanine as reference, the adjusted hazard ratio for the lowest IQ with risk of HF was 3.11 (95% confidence interval 2.60-3.71), corresponding to a hazard ratio of 1.32 (95% CI 1.28-1.35) per standard deviation decrease of IQ. This association proved persistent across predefined categories of HF with respect to pre-existing or concomitant co-morbidities; it was less apparent among obese conscripts (P for interaction =0.0004).In this study of young men, IQ was strongly associated with increased risk of early HF. The medical profession needs to be aware of this finding so as to not defer diagnosis.
14.	Lindgren, Martin, et al. (author) Elevated resting heart rate in adolescent men and risk of heart failure and cardiomyopathy. 2020 In: ESC heart failure. - : Wiley. - 2055-5822. ; 7:3, s. 1178-1185 Journal article (peer-reviewed)abstract This study aims to investigate the association of resting heart rate (RHR) measured in late adolescence with long-term risk of cause-specific heart failure (HF) and subtypes of cardiomyopathy (CM), with special attention to cardiorespiratory fitness.We performed a nation-wide, register-based cohort study of all Swedish men enrolled for conscription in 1968-2005 (n=1008363; mean age=18.3years). RHR and arterial blood pressure were measured together with anthropometrics as part of the enlistment protocol. HF and its concomitant diagnoses, as well as all CM diagnoses, were collected from the national inpatient, outpatient, and cause of death registries. Risk estimates were calculated by Cox-proportional hazards models while adjusting for potential confounders. During follow-up, there were 8400 cases of first hospitalization for HF and 3377 for CM. Comparing the first and fifth quintiles of the RHR distribution, the hazard ratio (HR) for HF associated with coronary heart disease, diabetes, or hypertension was 1.25 [95% confidence interval (CI)=1.13-1.38] after adjustment for body mass index, blood pressure, and cardiorespiratory fitness. The corresponding HR was 1.43 (CI=1.08-1.90) for HF associated with CM and 1.34 (CI=1.16-1.54) for HF without concomitant diagnosis. There was an association between RHR and dilated CM [HR=1.47 (CI=1.27-1.71)] but not hypertrophic, alcohol/drug-induced, or other cardiomyopathies.Adolescent RHR is associated with future risk of HF, regardless of associated aetiological condition. The association was strongest for HF associated with CM, driven by the association with dilated CM. These findings indicate a causal pathway between elevated RHR and myocardial dysfunction that warrants further investigation.
15.	Lindgren, Martin, et al. (author) Resting heart rate in late adolescence and long term risk of cardiovascular disease in Swedish men 2018 In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 259, s. 109-115 Journal article (peer-reviewed)abstract Aim: To investigate the association of resting heart rate (RHR) measured in late adolescence with the long term risk of myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), atrial fibrillation (AF), cardiovascular- and all-cause death. Methods and results: We followed a cohort of Swedish men enrolled for conscription in 1968–2005 (n = 1,008,485; mean age = 18.3 years) until December 2014. Outcomes were collected from the national inpatient - (IPR), outpatient - (OPR) and cause of death registries. Cox proportional hazard models were used to analyze the longitudinal association between RHR and outcomes while adjusting for potential confounders. While we found no independent association between RHR and risk of IS or MI when comparing the highest with the lowest quintile of the RHR distribution, but a positive association persisted between RHR and incident HF (Hazard ratio (HR) = 1.39 [95% confidence interval (CI) = 1.29–1.49]) after adjustment for body mass index (BMI) and blood pressure (BP). In similarly adjusted models, an inverse association was found for AF while there were weaker associations with death from cardiovascular disease (CVD) and all causes (adjusted HR = 1.12 [CI = 1.04–1.21] and 1.20 [CI = 1.17–1.24]). After further adjustment for cardiorespiratory fitness (CRF), the associations persisted for HF (HR = 1.26 [1.17–1.35] for any diagnostic position and HR = 1.43 [1.28–1.60] for HF as a main diagnosis) and for all-cause death (HR 1.09 [1.05–1.12]) but not for CVD death. Conclusion: Adolescent RHR is associated with future risk of HF and death, independently of BP, BMI and CRF, but not with CVD death, MI or IS, suggesting a causal pathway between elevated heart rate and myocardial dysfunction. © 2018 The Authors
16.	Lundgren, Markus, et al. (author) Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity 2017 In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1 Journal article (peer-reviewed)abstract Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
17.	Nyberg, Jenny, 1976, et al. (author) Anxiety severity and cognitive function in primary care patients with anxiety disorder: a cross-sectional study. 2021 In: BMC psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 21:1 Journal article (peer-reviewed)abstract Deficits in cognitive performance are reported in patients with anxiety disorders, but research is limited and inconsistent. We aimed to investigate cross-sectional associations between cognitive function, with focus on executive function, and anxiety severity in primary care patients diagnosed with anxiety disorders.189 Swedish patients aged 18-65years (31% men) with anxiety disorders diagnosed according to Mini International Neuropsychiatric Interview were included. Severity of anxiety was assessed using Beck Anxiety Inventory self-assessment scale. Digit span, block design and matrix reasoning tests from the Wechsler Adult Intelligence Scale IV, and the design fluency test from the Delis-Kaplan Executive Function System were used. Multivariable linear regression models were applied to investigate the relationship of anxiety severity and cognitive functioning. Comparisons were also performed to a normed non-clinical population, using the Wilcoxon signed rank test.More severe anxiety was associated with lower digit span test scores (R2=0.109, B=-0.040, p=0.018), but not with block design, matrix reasoning or design fluency tests scores, after adjustment for comorbid major depression in a multivariable model. When compared to a normed population, patients with anxiety performed significantly lower on the block design, digit span forward, digit span sequencing and matrix reasoning tests.Severity of anxiety among patients with anxiety disorder was associated with executive functions related to working memory, independently of comorbid major depression, but not with lower fluid intelligence. A further understanding of the executive behavioral control in patients with anxiety could allow for more tailored treatment strategies including medication, therapy and interventions targeted to improve specific cognitive domains.
18.	Nyberg, Jenny, 1976, et al. (author) Cardiovascular fitness and risk of migraine: A large, prospective population-based study of Swedish young adult men 2019 In: BMJ Open. - : BMJ. - 2044-6055. ; 9:8 Journal article (peer-reviewed)abstract Objectives To examine the longitudinal relationship between cardiovascular fitness in young adult men and future risk of migraine and to estimate eventual differential effects among categories of body mass index (BMI) and blood pressure. Design National, prospective, population-based cohort study. Setting Sweden 1968-2014. Participants 18-year-old Swedish men (n=1 819 828) who underwent mandatory military conscription examinations during the years 1968-2005. Primary and secondary outcomes The primary outcome was the first dispensation of prescribed migraine-specific medication, identified using the Swedish Prescribed Drug Register. The secondary outcome was documented migraine diagnosis from the Swedish National Hospital Register. Results During follow-up, 22 533 men filled a prescription for migraine-specific medication. After confounding adjustment, compared with high cardiovascular fitness, low and medium fitness increased the risk of migraine-specific medication (risk ratio (RR) low: 1.29, 95% CI 1.24 to 1.35; population attributable fraction: 3.6%, 95% CI 1.7% to 5.3% and RR medium: 1.15, 95% CI 1.12 to 1.19; population attributable fraction: 8.0%, 95% CI 4.0% to 11.7%). To assess potential effect measure modification, stratified analyses of these association by levels of BMI and blood pressure showed that lower fitness levels increased risk of migraine across all groups except among underweight men or men with high diastolic blood pressure. Conclusions Young men with a lower cardiovascular fitness had a higher long-term risk of developing pharmacological prescription-requiring migraine. This study contributes with information regarding risk factors for migraine in men, an understudied population in migraine research. © 2019 Author(s) (or their employer(s)).
19.	Nyberg, Jenny, 1976, et al. (author) Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study. 2018 In: Psychological medicine. - 1469-8978. ; 48:3, s. 416-425 Journal article (peer-reviewed)abstract Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship.Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life.Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers.Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.
20.	Nyberg, Jenny, 1976, et al. (author) Effects of exercise on symptoms of anxiety, cognitive ability and sick leave in patients with anxiety disorders in primary care: study protocol for PHYSBI, a randomized controlled trial 2019 In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 19:1 Journal article (peer-reviewed)abstract BackgroundAnxiety disorders are common and associated with reduced quality of life, impaired physical and mental health and an increased economic burden for society. While evidence exists for the effectiveness of exercise treatment for depression, there is a need for high-quality randomized clinical trials (RCT) with a focus on anxiety disorders. Further research is also warranted regarding outcomes of cognitive function, other health-related variables, dose-response effects, work ability and potential mechanisms.Method/designUsing a parallel, RCT design with three assessment points (baseline, post-intervention and one-year follow-up), we aim to assess the effect of a 12-week exercise intervention in primary care patients with anxiety disorders (n=180), diagnosed using the Mini International Neuropsychiatric Interview (M.I.N.I; Swedish version 6.0.0d DSM-IV). Participants are randomly assigned to three physical exercise groups: one low-intensity training group, one moderate- to high intensity training group and one control non-exercise group. Assessments include measures of anxiety symptoms, cognitive function, physical health variables such as cardiovascular fitness, sick-leave and levels of hormones/cytokines in blood samples.DiscussionFindings from this study will provide novel insights regarding the effects of exercise treatment on not only anxiety symptoms but also other outcomes including mental and physical health, cognitive function, dose-response effects, work ability/sick leave and on biomarkers that may help explain underlying mechanisms.Trial registrationThe trial was registered at ClinicalTrial.gov NCT03247270 August 8, 2017.
21.	Rosengren, Annika, 1951, et al. (author) Body weight in adolescence and long-term risk of early heart failure in adulthood among men in Sweden 2017 In: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:24, s. 1926-1933 Journal article (peer-reviewed)abstract AIMS: To study the relation between body mass index (BMI) in young men and risk of early hospitalization with heart failure. METHODS AND RESULTS: In a prospective cohort study, men from the Swedish Conscript Registry investigated 1968-2005 (n = 1 610 437; mean age, 18.6 years were followed 5-42 years (median, 23.0 years; interquartile range, 15.0-32.0), 5492 first hospitalizations for heart failure occurred (mean age at diagnosis, 46.6 (SD 8.0) years). Compared with men with a body mass index (BMI) of 18.5-20.0 kg/m2, men with a BMI 20.0-22.5 kg/m2 had an hazard ratio (HR) of 1.22 (95% CI, 1.10-1.35), after adjustment for age, year of conscription, comorbidities at baseline, parental education, blood pressure, IQ, muscle strength, and fitness. The risk rose incrementally with increasing BMI such that men with a BMI of 30-35 kg/m2 had an adjusted HR of 6.47 (95% CI, 5.39-7.77) and those with a BMI of >/=35 kg/m2 had an HR of 9.21 (95% CI, 6.57-12.92). The multiple-adjusted risk of heart failure per 1 unit increase in BMI ranged from 1.06 (95% CI, 1.02-1.11) in heart failure associated with valvular disease to 1.20 (95% CI, 1.18-1.22) for cases associated with coronary heart disease, diabetes, or hypertension. CONCLUSION: We found a steeply rising risk of early heart failure detectable already at a normal body weight, increasing nearly 10-fold in the highest weight category. Given the current obesity epidemic, heart failure in the young may increase substantially in the future and physicians need to be aware of this.
22.	Walser, Marion, 1961, et al. (author) Different modes of GH administration influence gene expression in the male rat brain 2014 In: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 222:2, s. 181-190 Journal article (peer-reviewed)abstract The endogenous secretion pattern in males of GH is episodic in rats and in humans, whereas GH administration is usually even. Different types of GH administration have different effects on body mass, longitudinal bone growth, and liver metabolism in rodents, whereas possible effects on brain plasticity have not been investigated. In this study, GH was administered as a continuous infusion or as two daily injections in hypophysectomized male rats. Thirteen transcripts previously known to respond to GH in the hippocampus and parietal cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH administration on several transcripts with different variations, and categories of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was applied. Accordingly, GH injections increased overall transcript abundance more than GH infusions (21% in the hippocampus, P<0.001 and 10% in the cortex, PZ0.09). Specifically, GH infusions and injections robustly increased neuronal hemoglobin beta (Hbb) expression significantly (1.8- to 3.6-fold), and GH injections were more effective than GH infusions in increasing Hbb in the cortex (41%, PZ0.02), whereas a 23% difference in the hippocampus was not significant. Also cortical connexin 43 was higher in the group with GH injections than in those with GH infusions (26%, P<0.007). Also, there were differences between GH injections and infusions in GH-related transcripts of the cortex (23%, PZ0.04) and glia-related transcripts of the hippocampus (15%, PZ0.02). Thus, with the exception of Hbb there is a moderate difference in responsiveness to different modes of GH administration. © 2014 Society for Endocrinology.
23.	Walser, Marion, 1961, et al. (author) Effects of peripheral administration of GH and IGF-I on gene expression in the hippocampus of hypophysectomised rats 2018 In: Neuroendocrinology Letters. - 0172-780X. ; 39:7, s. 525-531 Journal article (peer-reviewed)abstract OBJECTIVE: Growth hormone (GH) increases insulin-like growth factor I (IGF-I) production and both hormones affect hippocampal plasticity. We have previously shown that Hbb and Alas2 in the rat hippocampus were robustly regulated by GH-infusions for six days, whereas other transcripts were weakly affected. Here, weexplored the effects of prolonged GH administration on transcripts linked to neuroprotection and investigated whether serum IGF-I administration may exert similar effects. DESIGN: Hypophysectomised female rats were infused with GH or IGF-I for 19 days. Hbb, Alas2 and seven additional GH- and IGF-I-related transcripts were quantified by Q-RT-PCR in rat hippocampus. RESULTS: Three transcripts, Hbb, Alas2, and Aloxl5 were increased by both GH and IGF-I administration. The other transcripts were marginally affected. CONCLUSION: The 19-day GH-infusion induced similar effects as those reported after 6-day GH treatment, with the addition of the regulation of transcript Aloxl5. IGF-I induced altered gene expression in relation to its effect on weight gain. This study underlines that there is an entity of transcripts involved in neuroprotection and vascular tone that is regulated by both systemic GH and IGF-I. For other transcripts, the longer duration of this study did not significantly enhance the marginal effects of GH administration seen previously. © 2018 Neuroendocrinology Letters
24.	Walser, Marion, 1961, et al. (author) Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus. 2012 In: The Journal of endocrinology. - 1479-6805. ; 215:2, s. 257-68 Journal article (peer-reviewed)abstract GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2'-deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul)). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH.
25.	Walser, Marion, 1961, et al. (author) Mode of GH administration and gene expression in the female rat brain. 2017 In: The Journal of endocrinology. - 1479-6805. ; 233:2, s. 187-196 Journal article (peer-reviewed)abstract The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron-haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5'-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.
26.	Åberg, Daniel, 1973, et al. (author) Homeostasis model assessment of insulin resistance and outcome of ischemic stroke in non-diabetic patients - a prospective observational study 2019 In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 19:1 Journal article (peer-reviewed)abstract BackgroundInsulin resistance (IR) in relation to diabetes is a risk factor for ischemic stroke (IS), whereas less is known about non-diabetic IR and outcome after IS.MethodsIn non-diabetic IS (n=441) and controls (n=560) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), IR was investigated in relation to IS severity and functional outcome. IR was evaluated acutely and after 3months using the Homeostasis model assessment of IR (HOMA-IR). Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) after 3months, 2 and 7years. Associations were evaluated by logistic regression.ResultsHigher acute and 3-month HOMA-IR was observed in IS compared to the controls (both p<0.001) and in severe compared to mild IS (both p<0.05). High acute HOMA-IR was associated with poor outcome (mRS 3-6) after 3months and 7years [crude Odds ratios (ORs), 95% confidence intervals (CIs) 1.50, 1.07-2.11 and 1.59, 1.11-2.30, respectively], but not after 2years. These associations lost significance after adjustment for all covariates including initial stroke severity. In the largest IS subtype (cryptogenic stroke), acute HOMA-IR was associated with poor outcome after 2years also after adjustment for age and stroke severity (OR 2.86, 95% CI 1.01-8.12).ConclusionsIn non-diabetic IS patients, HOMA-IR was elevated and related to stroke severity, but after adjustment for IS severity, the associations between HOMR-IR and poor outcome lost significance. This could suggest that elevated IR mostly is a part of the acute IS morbidity. However, in the subgroup of cryptogenic stroke, the associations with poor outcome withstood correction for stroke severity.
27.	Åberg, Daniel, 1973, et al. (author) Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer's Disease 2015 In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 637-646 Journal article (peer-reviewed)abstract Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 levelwas increased inADmen versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
28.	Åberg, Daniel, 1973, et al. (author) Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study 2021 In: Life-Basel. - : MDPI AG. - 2075-1729. ; 11:6 Journal article (peer-reviewed)abstract Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56-3.49, and fully adjusted HR 1.64, 95% CI 1.02-2.61). In contrast, crude associations with poor functional outcome (mRS 3-6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.
29.	Åberg, Daniel, 1973, et al. (author) Serum IGF-I levels correlate to improvement of functional outcome after ischemic stroke. 2011 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:7 Journal article (peer-reviewed)abstract GH has positive cognitive effects when given to GH-IGF-I-deficient patients. GH and IGF-I exert both neuroprotective and regenerative effects on experimental stroke. We investigated whether the endogenous serum IGF-I (s-IGF-I) levels correlated with recovery of functional independence in patients who had suffered an ischemic stroke.
30.	Åberg, Daniel, 1973, et al. (author) Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study 2023 In: International Journal of Molecular Sciences. - 1422-0067. ; 24:11 Journal article (peer-reviewed)abstract Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor- I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
31.	Åberg, Maria A I, 1972, et al. (author) Body Weight in Adolescent Men in Sweden and Risk of an Early Acute Coronary Event: A Prospective Population-Based Study 2023 In: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12 Journal article (peer-reviewed)abstract BackgroundCoronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and ResultsThis was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m(2)), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m(2) had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. ConclusionsAn increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.
32.	Åberg, Maria A I, 1972, et al. (author) Cardiovascular fitness is associated with cognition in young adulthood. 2009 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. Journal article (peer-reviewed)abstract During early adulthood, a phase in which the central nervous system displays considerable plasticity and in which important cognitive traits are shaped, the effects of exercise on cognition remain poorly understood. We performed a cohort study of all Swedish men born in 1950 through 1976 who were enlisted for military service at age 18 (N = 1,221,727). Of these, 268,496 were full-sibling pairs, 3,147 twin pairs, and 1,432 monozygotic twin pairs. Physical fitness and intelligence performance data were collected during conscription examinations and linked with other national databases for information on school achievement, socioeconomic status, and sibship. Relationships between cardiovascular fitness and intelligence at age 18 were evaluated by linear models in the total cohort and in subgroups of full-sibling pairs and twin pairs. Cardiovascular fitness, as measured by ergometer cycling, positively associated with intelligence after adjusting for relevant confounders (regression coefficient b = 0.172; 95% CI, 0.168-0.176). Similar results were obtained within monozygotic twin pairs. In contrast, muscle strength was not associated with cognitive performance. Cross-twin cross-trait analyses showed that the associations were primarily explained by individual specific, non-shared environmental influences (>/=80%), whereas heritability explained <15% of covariation. Cardiovascular fitness changes between age 15 and 18 y predicted cognitive performance at 18 y. Cox proportional-hazards models showed that cardiovascular fitness at age 18 y predicted educational achievements later in life. These data substantiate that physical exercise could be an important instrument for public health initiatives to optimize educational achievements, cognitive performance, as well as disease prevention at the society level.
33.	Åberg, Maria A I, 1972, et al. (author) IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. 2003 In: Molecular and cellular neurosciences. - 1044-7431. ; 24:1, s. 23-40 Journal article (peer-reviewed)abstract The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)), showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling.
34.	Åberg, Maria A I, 1972, et al. (author) Nonpsychotic Mental Disorders in Teenage Males and Risk of Early Stroke A Population-Based Study 2016 In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 47:3, s. 814-821 Journal article (peer-reviewed)abstract Background and Purpose- Although the incidence of stroke is on the decline worldwide, this is not the case for early stroke. We aimed to determine whether nonpsychotic mental disorder at the age of 18 years is a risk factor for early stroke, and if adolescent cardiovascular fitness and intelligence quotient might attenuate the risk. Population-based Swedish cohort study of conscripts (n=1 163 845) who enlisted during 1968 to 2005. At conscription, 45 064 males were diagnosed with nonpsychotic mental disorder. Risk of stroke during follow-up (5-42 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses. There were 7770 first-time stroke events. In adjusted models, increased risk for stroke was observed in men diagnosed with depressive/neurotic disorders (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.37), personality disorders (HR, 1.52; 95% CI, 1.29-1.78), and alcohol/substance use disorders (HR, 1.61; 95% CI, 1.41-1.83) at conscription. Corresponding figures for fatal stroke were HR, 1.38; 95% CI, 1.06 to 1.79; HR, 2.26; 95% CI, 1.60 to 3.19; and HR, 2.20; 95% CI, 1.63 to 2.96. HRs for stroke were attenuated when fitness level and intelligence quotient were introduced. Associations remained significant for personality disorders and alcohol/substance use in the fully adjusted models. The interaction term was statistically significant for fitness but not for intelligence quotient. Our findings suggest that fitness may modify associations between nonpsychotic disorders and stroke. It remains to be clarified whether interventions designed to improve fitness in mentally ill youth can influence future risk of early stroke.
35.	Åberg, Maria A I, 1972, et al. (author) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. 2000 In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 20:8, s. 2896-903 Journal article (peer-reviewed)abstract In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.
36.	Åberg, N David, 1970, et al. (author) Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study 2018 In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 18:1 Journal article (peer-reviewed)abstract Background: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (Delta IGF-I, further transformed into Delta IGF-I-quintiles, Delta IGF-I-q) are associated with IS severity and outcome. Methods: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. Results: In general, the levels of s-IGF-I decreased (positive Delta IGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd Delta IGF-I-q showed the strongest association to mRS 0-2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18-11.9], and after 2 years, the 5th Delta IGF-I-q (OR 3.63, 95% CI 1.40-9.38) showed the strongest association to mRS 0-2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 031). Conclusions: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions.
37.	Åberg, N David, 1970, et al. (author) Diverging trends for onset of acute myocardial infarction, heart failure, stroke and mortality in young males: role of changes in obesity and fitness 2021 In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:2, s. 373-385 Journal article (peer-reviewed)abstract Background As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF). Objectives We investigated trends in early major CVD outcomes in a large cohort of young men. Methods Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21-year CVD event rates. Results 21-year CVD and all-cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971-1975 (reference), the hazard ratios (HRs) for the last 1991-1995 cohort were 0.50 [95% confidence interval (CI) 0.42-0.59] for CVD mortality; 0.57 (95% CI 0.54-0.60) for all-cause mortality; and 0.63 (95% CI 0.53-0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17-1.75), 1.30 (95% CI 1.01-1.68) and 1.84 (95% CI 1.47-2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately. Conclusion Secular trends of young-onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.
38.	Åberg, N David, 1970, et al. (author) Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1. 2013 In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 169:6, s. 759-65 Journal article (peer-reviewed)abstract In humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.
39.	Åberg, N David, 1970, et al. (author) Growth hormone and insulin-like growth factor I and cellular regeneration in the adult brain 2005 In: The Somatrotrophic Axis in brain Function. Editor Fred Nyberg. - : Elsevier. - 9780120884841 Book chapter (other academic/artistic)
40.	Åberg, N David, 1970, et al. (author) Influence of Cardiovascular Fitness and Muscle Strength in Early Adulthood on Long-Term Risk of Stroke in Swedish Men 2015 In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 46:7, s. 1769-1776 Journal article (peer-reviewed)abstract Background and Purpose Low cardiovascular fitness (fitness) in mid- and late life is a risk factor for stroke. However, the respective effects on long-term stroke risk of fitness and muscle strength in early adulthood are unknown. Therefore, we analyzed these in a large cohort of young men. Method We performed a population-based longitudinal cohort study of Swedish male conscripts registered in 1968 to 2005. Data on fitness (by the cycle ergometric test; n=1 166 035) and muscle strength (n=1 563 750) were trichotomized (low, medium, and high). During a 42-year follow-up, risk of stroke (subarachnoidal hemorrhage, intracerebral hemorrhage, and ischemic stroke) and fatality were calculated with Cox proportional hazards models. To identify cases, we used the International Classification of Diseases-Eighth to Tenth Revision in the Hospital Discharge Register and the Cause of Death Register. Results First-time stroke events were identified (subarachnoidal hemorrhage, n=895; intracerebral hemorrhage, n=2904; ischemic stroke, n=7767). For all stroke and fatality analysis any type of first-time stroke was recorded (n=10 917). There were inverse relationships in a dose-response fashion between fitness and muscle strength with any stroke (adjusted hazard ratios for the lowest, compared with the highest, tertile of each 1.70 [1.50-1.93] and 1.39 [1.27-1.53], respectively). There were stronger associations for fatal stroke. All 3 stroke types displayed similar associations. Associations between fitness and stroke remained when adjusted for muscle strength, whereas associations between muscle strength and stroke weakened/disappeared when adjusted for fitness. Conclusions At the age of 18 years, low fitness and to a lesser degree low muscle strength were independently associated with an increased future stroke risk.
41.	Åberg, N David, 1970, et al. (author) Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro. 2003 In: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 74:1, s. 12-22 Journal article (peer-reviewed)abstract Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.
42.	Åberg, N David, 1970, et al. (author) Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats. 2009 In: The Journal of endocrinology. - 1479-6805. ; 201:1, s. 141-50 Journal article (peer-reviewed)abstract IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdU-positive cells. (3)H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.
43.	Åberg, N David, 1970, et al. (author) Peripheral infusion of insulin-like growth factor-I increases the number of newborn oligodendrocytes in the cerebral cortex of adult hypophysectomized rats. 2007 In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3765-72 Journal article (peer-reviewed)abstract We have previously shown that recombinant human (rh) IGF-I induces cell proliferation and neurogenesis in the hippocampus of hypophysectomized rats. In the current investigation, we determined the effects of rhIGF-I on proliferation and differentiation in the cerebral cortex. Adult hypophysectomized rats were injected with bromodeoxyuridine (BrdU) to label newborn cells (once a day for the first 5 d), and rhIGF-I was administered peripherally for 6 or 20 d. In the cerebral cortex, the number of BrdU-labeled cells increased after 20 d but not after 6 d of rhIGF-I infusion. This suggests that rhIGF-I enhances the survival of newborn cells in the cerebral cortex. Using BrdU labeling combined with the oligodendrocyte-specific markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase, we demonstrated an increase in oligodendrogenesis in the cerebral cortex. The total amount of myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase was also increased on Western blots of homogenates of the cerebral cortex, confirming the immunohistochemical findings. Also, we observed an increase in the number of capillary-associated BrdU-positive cells, although total capillary area was not increased. rhIGF-I treatment did not affect cortical astrogliogenesis and neurogenesis was not observed. The ability of rhIGF-I to induce cortical oligodendrogenesis may have implications for the regenerative potential of the cortex.
44.	Åberg, N David, 1970, et al. (author) Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I 2020 In: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:3 Journal article (peer-reviewed)abstract Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (Delta IGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1-4, with PA1 representing sedentary and PA2-4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and Delta IGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (Delta IGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, Delta IGF-I increased by 9.7 (95% CI 1,1-18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to Delta IGF-I.
45.	Arcopinto, M., et al. (author) Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the TOSCA. GHD Study 2017 In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1 Journal article (peer-reviewed)abstract Background Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD. One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6 +/- 1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6 +/- 1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay. GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p=.008 and -24%, p=.015, respectively), lower LV end-systolic wall stress (-21%, p=.03), higher RV performance (+18% in RV area change, p=.03), lower estimated systolic pulmonary artery pressure (-11%, p=.04), higher peak VO2 (+20%, p=.001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p=.002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (beta = -1.92, SE = 1.67, p=.03), VE/VCO2 slope (beta = 2.23, SE = 1.20, p=.02) and NT-proBNP (beta = 2.48, SE = 1.02, p=.016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p<.001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF. GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.
46.	Barlind, Anna, 1978, et al. (author) The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus. 2010 In: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:1, s. 49-54 Journal article (peer-reviewed)abstract OBJECTIVE: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. DESIGN: In the present study, 10-day-old male mice received 6Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100mug/kg/day) for 28days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. RESULTS: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. CONCLUSION: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.
47.	Blomstrand, Fredrik, 1969, et al. (author) Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions. 1999 In: Neuroscience. - 0306-4522. ; 92:1, s. 255-65 Journal article (peer-reviewed)abstract Astrocytes are coupled via gap junctions, predominantly formed by connexin-43 proteins, into cellular networks. This coupling is important for the propagation of intercellular calcium waves and for the spatial buffering of K+. Using the scrape-loading/dye transfer technique, we studied gap junction permeability in rat astrocytes cultured from four different brain regions. The cultures were shown to display regional heterogeneity with the following ranking of the gap junction coupling strengths: hippocampus = hypothalamus > cerebral cortex = brain stem. Similar relative patterns were found in connexin-43 messenger RNA and protein levels using solution hybridization/RNase protection assay and western blots, respectively. The percentages of the propagation area of mechanically induced intercellular calcium waves for cortical, brain stem and hypothalamic astrocytes compared with hippocampal astrocytes were approximately 77, 42, and 52, respectively. Thus, the extent of calcium wave propagation was due to more than just gap junctional permeability as highly coupled hypothalamic astrocytes displayed relatively small calcium wave propagation areas. Incubation with 5-hydroxytryptamine decreased and incubation with glutamate increased the calcium wave propagation area in hippocampal (67% and 170% of the control, respectively) and in cortical astrocytes (82% and 163% of the control, respectively). Contrary to hippocampal and cortical astrocytes, the calcium wave propagation in brain stem astrocytes was increased by 5-hydroxytryptamine incubation (158% of control), while in hypothalamic astrocytes, no significant effects were seen. Similar effects from 5-hydroxytryptamine or glutamate treatments were observed on dye transfer, indicating an effect on the junctional coupling strength. These results demonstrate a strong relationship between connexin-43 messenger RNA levels, protein expression, and gap junction permeability among astroglial cells. Furthermore, our results suggest heterogeneity among astroglial cells from different brain regions in intercellular calcium signaling and in its differential modulation by neurotransmitters, probably reflecting functional requirements in various brain regions.
48.	Brännmark, Cecilia, et al. (author) FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke 2023 In: Bmj Open. - 2044-6055. ; 13:5 Journal article (peer-reviewed)abstract ntroduction Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the FIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery. Methods and analysis We recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers. Ethics and dissemination FIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets.
49.	D'Assante, R., et al. (author) Myocardial expression of somatotropic axis, adrenergic signalling, and calcium handling genes in heart failure with preserved ejection fraction and heart failure with reduced ejection fraction 2021 In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:2, s. 1681-1686 Journal article (peer-reviewed)abstract Aims Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes. Methods and results Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n = 6) and HFpEF (n = 7) and healthy subjects (n = 9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-alpha. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102 +/- 35.6, 138 +/- 11.5, and 160 +/- 13.2 ng/mL, P < 0.001, respectively). At myocardial level, HFrEF showed significant decreased GHR and increased IGF-1R expressions when compared with HFpEF and controls (0.54 +/- 0.27, 0.94 +/- 0.25, and 0.84 +/- 0.2, P < 0.05 and 1.52 +/- 0.9, 1.06 +/- 0.21, and 0.72 +/- 0.12, P < 0.05, respectively), while no differences in the local expression of IGF-1 mRNA were detected among the groups (0.80 +/- 0.45, 0.97 +/- 0.18, and 0.63 +/- 0.23, P = 0.09, respectively). With regard to calcium handling and adrenergic signalling, HFrEF displayed significant decreased levels of SERCA2 (0.19 +/- 0.39, 0.82 +/- 0.15, and 0.87 +/- 0.32, P < 0.01) and increased levels of GRK2 (3.45 +/- 2.94, 0.93 +/- 0.12, and 0.80 +/- 0.14, P < 0.01) and GRK5 (1.32 +/- 0.70, 0.71 +/- 0.14, and 0.77 +/- 0.15, P < 0.05), while no significant difference was found in ADRB1 (0.66 +/- 0.4, 0.83 +/- 0.3, and 0.86 +/- 0.4) and ADRB2 mRNA expression (0.65 +/- 0.3, 0.66 +/- 0.2, and 0.68 +/- 0.1) when compared with HFpEF and controls. Finally, no changes in the local expression of TNF-alpha were detected among groups. Conclusions Heart failure with reduced ejection fraction and HFpEF patients with stable clinical condition display a distinct molecular milieu of genes involved in somatotropic axis regulation, calcium handling, and adrenergic derangement at a myocardial level. The unique opportunity to compare these results with a control group, as reference population, may contribute to better understand HF pathophysiology and to identify novel potential therapeutic targets that could be modulated to improve ventricular function in patients with HF.
50.	Erlandsson, Malin, 1972, et al. (author) Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis 2019 In: BMC Med. - : Springer Science and Business Media LLC. - 1741-7015. ; 17:1 Journal article (peer-reviewed)abstract ObjectivesSince low insulin-like growth factor (IGF) 1 is often linked to inflammation, we analyze whether serum levels of IGF1 are associated with cardiovascular disease (CVD) in rheumatoid arthritis (RA) in a longitudinal observational study.MethodsA CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52years) and in 132 female patients after ischemic stroke (mean age 56years) with no rheumatic disease, using the Framingham algorithm. The median level of IGF1 divided the cohorts in IGF1(high) and IGF1(low) groups. A 5-year prospective follow-up for new CVD events was completed in all RA patients. The Mantel-Cox analysis and event-free survival curves were prepared. Unsupervised clustering of proteins within the IGF1 signaling pathway was employed to identify their association with eCVR.ResultsLow IGF1 resulted in a higher eCVR in RA patients (7.2% and 3.3%, p=0.0063) and in stroke (9.3% and 7.1%, p=0.033). RA had higher rate for new CVD events at prospective follow-up (OR 4.96, p=0.028). Hypertension was the major risk factor associated with low IGF1 in RA and stroke. In hypertension, IGF1 was no longer responsible for intracellular activation and lost its correlation to IRS1/2 adaptor proteins. The clustering analysis confirmed that combination of low IGF1 and IRS1/2 with high IL6, insulin, and glucose predisposed to high eCVR and emphasized the functional role of serum IGF1.ConclusionsLow serum IGF1 precedes and predicts development of early CVD events in female RA patients. Hypertension and aberrant IGF1 receptor signaling are highlighted as the important contributors to IGF1-related CVD events.

Skapa referenser, mejla, bekava och länka

Permalink

Result 1-50 of 85

Refine your search

Type of publication: journal article (78); conference paper (2); book chapter (2); reports (1); doctoral thesis (1); research review (1); show more...; show less...

Type of content: peer-reviewed (81); other academic/artistic (4)

Author/Editor: Åberg, N David, 1970 (78); Isgaard, Jörgen, 195 ... (34); Åberg, Maria A I, 19 ... (31); Svensson, Johan, 196 ... (20); Kuhn, Hans-Georg, 19 ... (19); Jood, Katarina, 1966 (15); show more...; Waern, Margda, 1955 (14); Jern, Christina, 196 ... (14); Eriksson, Peter S, 1 ... (12); Rosengren, Annika, 1 ... (11); Nyberg, Jenny, 1976 (11); Åberg, Daniel, 1973 (11); Torén, Kjell, 1952 (10); Blomstrand, Christia ... (10); Nilsson, Michael, 19 ... (10); Blennow, Kaj, 1958 (9); Zetterberg, Henrik, ... (9); Walser, Marion, 1961 (9); Lindgren, Martin (8); Rönnbäck, Lars, 1951 (7); Oscarsson, Jan, 1960 (7); Schiöler, Linus, 197 ... (7); Schaufelberger, Mari ... (7); Wall, Alexander (7); Nilsson, M (6); Robertson, Josefina (6); Walker, F. R. (6); Adiels, Martin, 1976 (5); Kristensson, Gerhard (5); Andreasson, Ulf, 196 ... (5); Stanne, Tara M, 1979 (5); Henriksson, Malin (5); Wall, David J N (5); Åberg, Ingegerd (5); Wallin, Anders, 1950 (4); Redfors, Petra (4); Oxelmark, Lena (4); Eggertsen, Robert, 1 ... (4); Erichsen Andersson, ... (4); Danielsson, Louise, ... (4); Crock, P. (4); Bergh, Ylva (4); Ong, L. K. (4); Milton, Jenny, 1974 (4); Hansson, Elisabeth, ... (3); Lind, Johan (3); Djekic, Demir (3); Gillespie, B. M. (3); Gadd, Gustaf (3); Sanchez-Bezanilla, S ... (3); show less...

University: University of Gothenburg (78); Lund University (6); Karolinska Institutet (6); Chalmers University of Technology (2); Umeå University (1); Örebro University (1); show more...; Linköping University (1); Högskolan Dalarna (1); show less...

Language: English (85)

Research subject (UKÄ/SCB): Medical and Health Sciences (74); Engineering and Technology (5); Natural sciences (3); Social Sciences (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Copy and save the link in order to return to this view