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Simple Summary: Individuals treated for brain tumors in childhood are at high risk of cognitive and other late complications. The aim of this nationwide registry study was to explore further education following the nine years of compulsory school in Sweden in teenagers and young adults treated for childhood brain tumors. Individuals treated for embryonal tumors, low grade astrocytomas, optic pathway gliomas, craniopharyngiomas, and neuronal and mixed neuronal–glial tumors, were analyzed separately. All individuals treated for brain tumors were compared to about five times as many matched controls without cancer diagnoses or treatments. Our results demonstrate significant differences between cases and controls regarding attendance in high school, folk high school, and university. Individuals treated for embryonal tumors or optic pathway gliomas attended post-compulsory education less frequently than other analyzed diagnoses. There was a positive correlation between parental education levels and attendance in high school and university for both cases and controls. The risk of late complications after a brain tumor in childhood is high. Both the tumor itself and the treatments give rise to sequelae that affect daily life activities. In this registry study, we explored post-compulsory education, i.e., further education following the nine compulsory years in school, in 452 cases born 1988–1996 and diagnosed with a brain tumor before their fifteenth birthday. They were compared with 2188 individual controls who were not treated for cancer. Significantly fewer teenagers and young adults treated for brain tumors in childhood attended high school or university compared with controls, especially individuals treated for embryonal tumors or optic pathway gliomas. A significantly larger proportion of subjects treated for embryonal tumors and craniopharyngiomas attended folk high schools, a type of post-compulsory school with a more accessible learning environment. For both cases and controls, we observed a positive correlation between parental education levels and attendance in high school and university. In our previous studies we have shown that children treated for brain tumors, as a group, tend to perform worse during their last year of compulsory school compared with their peers, and the current study confirms that these differences remain over time. [ABSTRACT FROM AUTHOR]

Recurrent headache, abdominal and musculoskeletal pain are common in adolescents and it is therefore important to understand their impact on the transitional period from childhood to adulthood. However, studies of the prevalence over time and implications on educational outcomes are still limited, especially regarding multiple pain symptoms. The present study material consists of questionnaire surveys, completed in 2000 and 2008, including two study populations of 9th grade adolescents aged 15 living in West Sweden (n = 20 877). Pain symptoms and demographic variables were based on self-reports from the questionnaires, and school grades were obtained from Statistics Sweden after the student had finished their 9th grade. Between 2000 and 2008, the prevalence of abdominal pain increased among Swedish adolescents (largest increase in girls); the prevalence of headache increased only in girls; the prevalence of pain in upper body decreased only in boys. School grades were significantly lower among those with headache or abdominal pain. Among students with low school grades (10th percentile) the estimated difference between those having any of the symptoms or none were -27 school grade units (95% confidence interval for girls (-27.8; -26.0), for boys (-27.6; -25.5). Both symptoms being present pronounced the association. Low parental education increased the negative effect of symptoms on school grades, most pronounced in the group with the lowest grades. In conclusion, identification of pain symptoms may improve academic achievements, especially in students with multiple symptoms and with parents having low education. Further intervention studies are need. [ABSTRACT FROM AUTHOR]

Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16-25, n = 1,819,817) who enlisted 1968-2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n = 526) during up to 46 years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p = 0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01-1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93-0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92-0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk. [ABSTRACT FROM AUTHOR]

Background: Survivors of pediatric brain tumors are at high risk of late complications that may affect their daily life in both short‐ and long‐term perspectives. Methods: In this nationwide registry‐based study we explored the occupational outcomes, including employment, sickness or activity compensation and parental leave, in 452 individuals in Sweden, born 1988–1996, and diagnosed with a brain tumor before their 15th birthday. Their results were compared with 2188 matched controls. Results: There were significant differences between cases and controls for all assessed variables. The cases had benefitted from sickness or activity compensation 11 times more often than controls (CI 7.90–15.83; p < 0.001) between 2005 and 2016. Controls were almost three times more likely to have an employment (OR 0.36; CI 0.28–0.47; p < 0.001) and nearly twice as likely to have been on parental leave (OR 0.56; CI 0.39–0.80; p = 0.002). Although cases treated for high‐grade tumors typically fared worse than those treated for low‐grade tumors, significant differences for all assessed variables were also observed for cases treated for a low‐grade tumor compared with controls. Conclusions: Our findings emphasize the need for follow‐up programs for all brain tumor diagnoses, not only those known to be at most risk. This is evident, for example, from the high number of cases who received sickness or activity compensation. [ABSTRACT FROM AUTHOR]

Little is known about common risk factors for early-onset dementia. In a population-based cohort study of over 1.1 million males, followed for up to 42 years, Nyberg et al. reveal that lower cardiovascular and/or cognitive fitness in early adulthood is associated with increased risk of early-onset dementia later in life.Patients with early-onset dementia are a significantly under-recognized subgroup of patients with an increasing prevalence. Epidemiological studies are limited and studies of modifiable risk factors, such as physical fitness, are lacking. We aimed to investigate the associations between cardiovascular fitness individually and in combination with cognitive performance at age 18 and risk of early-onset dementia and mild cognitive impairment later in life. We performed a population-based cohort study of over 1.1 million Swedish, 18-year-old, male conscripts, who underwent conscription exams between 1968 and 2005. These males were then followed for up to 42 years. Objective data on cardiovascular fitness and cognitive performance were collected during conscription exams and were subsequently linked with hospital registries to calculate later risk of early-onset dementia and mild cognitive impairment using Cox proportional hazards models controlling for several confounders. The scores from the exams were divided into tertiles (low, medium, high) for the analyses. The mean follow-up time for the analyses was 25.7 years (standard deviation: 9.3) and the median was 27 years. In total, 30 195 315 person-years of follow-up were included in the study. In fully adjusted models, both low cardiovascular fitness and cognitive performance (compared to high) at age 18 were associated with increased risk for future early-onset dementia (cardiovascular fitness, n = 662 events: hazard ratio 2.49, 95%, confidence interval 1.87–3.32; cognitive performance, n = 657 events: hazard ratio 4.11, 95%, confidence interval 3.19–5.29) and mild cognitive impairment (cardiovascular fitness, n = 213 events: hazard ratio 3.57, 95%, confidence interval 2.23–5.74; cognitive performance, n = 212 events: hazard ratio 3.23, 95%, confidence interval 2.12–4.95). Poor performance on both cardiovascular fitness and cognitive tests was associated with a >7-fold (hazard ratio 7.34, 95%, confidence interval 5.08–10.58) and a >8-fold (hazard ratio 8.44, 95%, confidence interval 4.64–15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance. [ABSTRACT FROM PUBLISHER]

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% Cl, 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 l8y 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. [ABSTRACT FROM AUTHOR]

Aim: Fish intake is reported to positively influence cognitive performance in infants and the elderly. In a longitudinal cohort study, we evaluated how fish consumption related to later cognitive performance in healthy young male adolescents. Methods: In 2000, all 15-year-olds (n = 18 158; 9260 males) in the western region of Sweden were requested to complete an extensive questionnaire with items on diseases, fish consumption and socioeconomic status. Questionnaire data from the male responders (n = 4792, response rate 52%) were linked with records on subsequent intelligence test performance at age 18 from the Swedish Military Conscription Register (n = 3972). Multivariate linear models were used to estimate associations between fish intake and cognitive performance, adjusting for potential confounders. Results: There was a positive association between the number of times having fish meals per week at age 15 and cognitive performance measured 3 years later. Fish consumption of more than once per week compared to less than once per week was associated with higher stanine scores in combined intelligence (0.58 units; 95% confidence interval 0.39, 0.76), in verbal performance (0.45; 0.27, 0.63) and in visuospatial performance (0.50; 0.31, 0.69). The association between fish consumption and the 3 intelligence scores was the same in lowly and highly educated groups. This indicates that education did not influence the association between the frequency of fish meals consumed and cognitive performance. Conclusion: Frequent fish intake at age 15 was associated with significantly higher cognitive performance 3 years later. [ABSTRACT FROM AUTHOR]

Abstract: MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA. [Copyright &y& Elsevier]

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 (p70S6K), 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. [Copyright &y& Elsevier]

In most brain regions of highly developed mammals, the majority of neurogenesis is terminated soon after birth. However, new neurons are continually generated throughout life in the subventricular zone and the dentate gyrus of the hippocampus. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that has demonstrated effects on these progenitor cells. IGF-I induces proliferation of isolated progenitors in culture, as well as affecting various aspects of neuronal induction and maturation. Moreover, systemic infusion of IGF-I increases both proliferation and neurogenesis in the adult rat hippocampus, and uptake of serum IGF-I by the brain parenchyma mediates the increase in neurogenesis induced by exercise. Neurogenesis in the adult brain is regulated by many factors including aging, chronic stress, depression and brain injury. Aging is associated with reductions in both hippocampal neurogenesis and IGF-I levels, and administration of IGF-I to old rats increases neurogenesis and reverses cognitive impairments. Similarly, stress and depression also inhibit neurogenesis, possibly via the associated reductions in serotonin or increases in circulating glucocorticoids. As both of these changes have the potential to down regulate IGF-I production by neural cells, stress may inhibit neurogenesis indirectly via downregulation of IGF-I. In contrast, brain injury stimulates neurogenesis, and is associated with upregulation of IGF-I in the brain. Thus, there is a tight correlation between IGF-I and neurogenesis in the adult brain under different conditions. Further studies are needed to clarify whether IGF-I does indeed mediate neurogenesis in these situations. [Copyright &y& Elsevier]

Exercise interventions show promise in the treatment of anxiety disorders, but effects on health-related quality of life (HR-QoL), work ability, and sick leave are little studied. We investigated these outcomes in a 12-week randomized controlled trial with a 1-year follow-up. Patients aged 18–65 (n = 222) with anxiety disorders from primary care centers in Gothenburg were randomized to a control group or one of two 12-week exercise intervention groups (low-intensity, [LI] and moderate/high-intensity, [HI]); 148 were evaluated at 12-weeks and 113 completed the 1-year follow-up. The EuroQol 5D (EQ5D; index and the visual analogue scale [VAS]), work ability score (WAS), presenteeism, and self-reported sick leave were assessed at baseline, 12 weeks, and 1 year. Improvements were defined by binary cut-offs for each scale. Binary logistic regression with odds ratios (OR) and 95 % confidence intervals (CI) were reported. There were improved scores for EQ5D and WAS in the HI group compared to controls after 12 weeks (EQ5D index: 4.74 [1.91–11.7], EQ5D-VAS 4.00, [1.65–9.72], WAS 3.41 [1.24–7.37]) and 1 year (EQ5D index: 3.05 [1.05–8.81], EQ5D-VAS 3.20 [1.16–8.84], WAS 5.50 [1.85–16.3]). Post-hoc analysis showed higher ORs in participants on antidepressants (n = 75) (12-week EQ5D index: OR 9.95 [2.85–34.8]) and significant improvements in EQ5D scores for both intervention groups after 1 year. There were no between-group differences for presenteeism or sick leave. Discontinuation was high, mostly early after randomization (n = 74), as is common for anxiety interventions. HI Exercise improves HR-QoL and work ability in anxiety patients, especially when combined with antidepressants. • High-intensity exercise improves health-related quality of life and work ability with long-lasting effects after 1 year. • There were trends suggesting a dose-response effect of exercise on health-related quality of life and work ability. • Exercise effects are greater in patients with antidepressant medication. • There were no between-group differences for presenteeism or sick leave. [ABSTRACT FROM AUTHOR]

Simple Summary: It has been shown that lifestyle factors such as smoking, alcohol consumption, diet, and physical activity affect the risk of developing cancer in older adults. While this is not the case for childhood cancers, survivors of childhood cancer are at increased risk of developing cancer in adulthood, called subsequent malignant neoplasms, due to the cancer treatment they received in childhood. We aimed to assess whether the risk of developing subsequent malignant neoplasms in young adulthood was associated with lifestyle factors. We could not see any association between lifestyle factors and subsequent malignant neoplasms in young adult childhood cancer survivors. This suggests that while lifestyle has other health benefits, it is possible that the risk of subsequent malignant neoplasms in young adult childhood cancer survivors cannot be modified with lifestyle behaviors. Introduction: This study aimed to assess longitudinal associations between lifestyle and subsequent malignant neoplasms (SMNs) in young adult childhood cancer survivors. Methods: Members of the St. Jude Lifetime Cohort (SJLIFE) aged ≥18 years and surviving ≥5 years after childhood cancer diagnosis were queried and evaluated for physical activity, cardiorespiratory fitness (CRF), muscle strength, body mass index (BMI), smoking, risky drinking, and a combined lifestyle score. Time to first SMN, excluding nonmalignant neoplasms and nonmelanoma skin cancer, was the outcome of longitudinal analysis. Results: Survivors (n = 4072, 47% female, 29% smokers, 37% risky drinkers, 34% obese, and 48% physically inactive) had a mean (SD) time between baseline evaluation and follow-up of 7.0 (3.3) years, an age of 8.7 (5.7) years at diagnosis, and an age of 30 (8.4) years at baseline lifestyle assessment. Neither individual lifestyle factors nor a healthy lifestyle score (RR 0.8, 0.4–1.3, p = 0.36) were associated with the risk of developing an SMN. Conclusions: We did not identify any association between lifestyle factors and the risk of SMN in young adult childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Non-fatal self-harm (SH) is a major risk factor for late-life suicide. A better knowledge of the clinical management of older adults who self-harm is needed to establish where improvements could be made for the implementation of effective suicide prevention interventions. We therefore assessed contacts with primary and specialised care for mental disorders and psychotropic drug use during the year before and after a late-life non-fatal SH episode. Longitudinal population-based study in adults aged ≥75 years with SH episode between 2007 and 2015 retrieved from the regional database VEGA. Healthcare contacts for mental disorders and psychotropic use were assessed during the year before and after the index SH episode. There were 659 older adults who self-harmed. During the year before SH, 33.7% had primary care contacts with a mental disorder, 27.8% had such contacts in specialised care. Use of specialised care increased sharply after the SH, reaching a maximum of 68.9%, but this figure dropped to 19.5% by the end of the year. Use of antidepressants increased from 41% before to 60% after the SH episode. Use of hypnotics was extensive before and after SH (60%). Psychotherapy was rare in both primary and specialised care. The use of specialised care for mental disorders and antidepressant prescribing increased after SH. The drop in long-term healthcare visits should be further explored to align primary and specialised healthcare to the needs of older adults who self-harmed. The psychosocial support of older adults with common mental disorders needs to be strengthened. [ABSTRACT FROM AUTHOR]

Background Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic. Methods In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017–19 in the whole Swedish population. Results COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65–110 years and women aged 75–110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020. Conclusions Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19. [ABSTRACT FROM AUTHOR]

Background: Our aim was to assess associations between cardiorespiratory fitness (CRF) and body mass index (BMI) in youth and 5‐year mortality after site‐specific cancer diagnoses in men. Methods: Men with cancer from a population who underwent military conscription at ages 16–25 during 1968–2005 in Sweden were included. CRF was assessed as maximal aerobic workload on a cycle ergometer test and was classified as low, moderate, or high. BMI (kg/m2) was classified as underweight (<18.5), normal weight (18.5–24.9), overweight (25–29.9), or obesity (>30). Conscription data were linked with register data on cancer diagnosis and mortality. Analyses included CRF, BMI, date of diagnosis, and age, year, and center for conscription. Results: A total of 84,621 cancer cases were included. Mean age at diagnosis was 52 years. Follow‐up data were available during a mean of 6.5 years. There were linear protective associations between CRF and mortality after any cancer diagnosis (hazard ratio [HR] for high vs. low CRF 0.70), malignant skin cancer (HR 0.80), non‐Hodgkin lymphoma (HR 0.78), and cancer in the lungs (HR 0.80), head and neck (HR 0.68), pancreas (HR 0.83), stomach (HR 0.78), liver (HR 0.84), rectum (HR 0.79), and bladder (HR 0.71). Overweight and/or obesity were associated with increased mortality after any cancer (HR for obesity vs. normal weight 1.89), malignant skin cancer (HR 2.03), Hodgkin lymphoma (HR 2.86) and cancer in the head and neck (HR 1.38), thyroid (HR 3.04), rectum (HR 1.53), kidney (HR 1.90), bladder (HR 2.10), and prostate (HR 2.44). Conclusion: We report dose‐dependent associations between CRF and BMI in youth and mortality after site‐specific cancer diagnoses in men. The associations with mortality could be due to both cancer inhibition and an improved tolerance to withstand cancer treatment. These results strengthen the incentive for public health efforts aimed at establishing a high CRF and normal weight in youth. [ABSTRACT FROM AUTHOR]

Background: Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population‐attributable fractions (PAFs) of multiple medical and social exposures for COVID‐19 outcomes have not been evaluated among older adults. Objectives: We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. Methods: We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. Results: Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS‐CoV‐2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long‐term care was 98.8% among persons aged 55–64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long‐term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8–9.1) and 22.5 (95% CI 19.6–25.7) for mortality, with PAFs of 21.9% (95% CI 20.9–22.9) and 33.3% (95% CI 32.4–34.3), respectively. Conclusion: Among Swedish residents aged 55 years and above, those with home care or long‐term care had markedly increased risk for COVID‐19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the study "CNTF Induces Gliogenesis via the JAK-STAT Signaling Pathway in Adult CNS Progenitor Cells." The study examined the effect of CNTF on hippocampal progenitors derived from adult rats. It found that CNTF is an inducer of astrocytic commitment in multipotent progenitors from the adult CNS and it differentiates along the glial lineage through the JAK-STAT signaling pathway.

While the detrimental effects of cranial radiotherapy on the developing brain are well known, the effects on cognitive performance of low doses of ionizing radiation is less studied. We performed a population-based cohort study to determine whether low doses of ionizing radiation to the brain in infancy affects cognitive function later in life. Further we hypothesized that the dose to the hippocampus predicts cognitive late side effects better than the anterior or the posterior brain doses. Material and methods. During 1950-1960 3860 boys were treated with radiation in Sweden for cutaneous hemangiomas before the age of 18 months. Of these, 3030 were analyzed for military test scores at the age of 18 years and 2559 for the highest obtained educational level. Results. Logical, spatial and technical test scores were not affected by increasing irradiation doses. The verbal test scores displayed a significant trend for decreasing scores with increasing doses to the hippocampus (p = 0.005). However, the absolute mean difference between the zero dose and the highest dose category (median 680 mGy) was very small, only 0.64 stanine points, and the significance was dependent on the highest dose category, containing few subjects. The educational level was not affected by brain irradiation. Overall, the hippocampal dose was a better predictor of late cognitive side effects than the doses to the anterior or the posterior brain. In conclusion, there was no decrease in logical, spatial and technical verbal or global test scores after ionizing radiation doses up to 250 mGy, but a subtle decrease in verbal test scores if the highest dose category was included (median 680 mGy). However, the clinical relevance of this decline in the highest dose group is questionable, since we could not find any effect on the highest obtained educational level. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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.Limitations: The use of self-rating measures which bears the risk of an under- or overestimation of symptoms.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 189 Swedish patients aged 18–65 years (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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract: Treatment with a kappa-opioid receptor agonist for 5 days decreases locomotor activity and reduces activity in response to a cocaine challenge 3 days later. In addition, chronic cocaine increases kappa-opioid receptor density, striatal dynorphin, and dynorphin gene expression in the striatum. The upregulation of kappa-opioid receptors after cocaine treatment occurs predominantly in brain regions that are highly innervated by serotonin. To determine if serotonin plays a role in the effects of kappa-opioid receptor agonists on cocaine-stimulated activity, parachloroamphetamine (PCA), which depleted serotonin by 53%–66%, or saline, was given prior to a five-day treatment with U-69593 or vehicle. Three days later each rat received a single injection of cocaine and locomotor activity was measured. Treatment with PCA had no effect on the ability of U-69593 alone to decrease locomotor activity. Thus, the behavioral effects of U-69593 alone were not dependent upon serotonin. In rats pretreated with saline, U-69593 treatment significantly blocked the locomotor-activating effects of cocaine. Following PCA pretreatment, however, there were no significant differences in locomotor activity in rats challenged with an injection of cocaine after treatment with U-69593 or vehicle. Thus, serotonin depletion prevented the long-lasting blockade of the locomotor-activating effects of cocaine subsequent to repeated administration of U-69593 but did not alter the effects of cocaine in rats that were treated with vehicle. Thus, the effects of PCA on U-69593 are not due to non-specific alterations in cocaine-induced locomotor activity. These findings suggest that serotonin plays an important role in mediating the effects of kappa-opioid receptor agonists on the behavioral response to cocaine. [Copyright &y& Elsevier]

Systemic inflammation may be implicated in the pathophysiology of Parkinson's disease (PD). Since PD occurs usually in later life, most studies of causal factors are conducted in older populations, so potentially important influences from early life cannot be adequately captured. We investigated whether the erythrocyte sedimentation rate (ESR) in early adulthood is associated with the subsequent development of PD in men. As part of Swedish national conscription testing conducted from 1968 through 1983 (N = 716,550), the erythrocyte sedimentation rate, as a measure of inflammation, was measured in 659,278 young men. The cohort was observed for subsequent PD events (N = 1513) through December 2016. Cox proportional hazards models were used to estimate the hazard ratios (HR) with 95% CI with adjustment for potential confounders. Individuals with higher ESRs were significantly less likely to be diagnosed with PD, as ESR was linearly and inversely associated with PD risk. The magnitude of the association between ESR and PD risk was similar for increases up to 15 mm/h, leveled off thereafter, and was non-significant for ESR values > 20 mm/h. The HR for PD with basic adjustments (age at conscription, year of conscription, test center and erythrocyte volume fraction) was 0.94 (95% CI 0.89–0.99, P = 0.02) per log2 increase in ESR, corresponding to a two-fold increase in ESR. Further adjustments for potential confounders (parental education, systolic and diastolic blood pressures, and IQ) scarcely altered the HR. The results suggest a prospective association between high ESR and reduced risk for PD. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic immune-mediated disease and psoriatic arthritis is a common coexisting condition. Cardiorespiratory fitness is the overall capacity to perform exertion exercise. Low levels of cardiorespiratory fitness are associated with negative health outcomes. Individuals with psoriasis have lower cardiorespiratory fitness compared with individuals without psoriasis. There are no previous studies exploring the association between cardiorespiratory fitness and new-onset psoriasis and psoriatic arthritis. Methods: With the objective to investigate whether low cardiorespiratory fitness in late adolescence increases the risk for onset of psoriasis and psoriatic arthritis, a cohort of Swedish men in compulsory military service between 1968 and 2005 was created using data from the Swedish Military Service Conscription Register. Cardiorespiratory fitness, estimated by maximum capacity cycle ergometer testing at conscription, was divided into three groups: high, medium, and low. Diagnoses were obtained using the Swedish National Patient Register and cohort members were followed from conscription until an event, new-onset psoriasis or psoriatic arthritis, occurred, or at the latest until 31 December 2016. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios with 95% confidence intervals for incident psoriasis and psoriatic arthritis. Results: During the follow-up period (median follow-up time 31 years, range 0–48 years), 20,679 cases of incident psoriasis and 6,133 cases of incident psoriatic arthritis were found among 1,228,562 men (mean age at baseline 18.3 years). There was a significant association between low cardiorespiratory fitness and incident psoriasis and psoriatic arthritis (hazard ratio 1.35 (95% confidence interval 1.26–1.44) and 1.44 (95% confidence interval 1.28–1.63), respectively). Conclusions: These novel findings suggest that low cardiorespiratory fitness at an early age is associated with increased risk of incident psoriasis and psoriatic arthritis among men, and highlight the importance of assessing cardiorespiratory fitness early in life. [ABSTRACT FROM AUTHOR]

Background: High education level and high occupational complexity have been implicated as risk factors for Parkinson's disease (PD). Objective: The objective was to determine whether cognitive capacity, measured as IQ, in early adulthood is associated with the subsequent development of PD. Method: Data on IQ were retrieved from the Swedish Military Service Conscription Registry, comprising Swedish males who enlisted for military service in the period 1968–1993 (N = 1,319,235). After exclusion, 1,189,134 subjects in total were included in the present study. Individuals who later developed PD (N = 1,724) were identified using the Swedish National Patient Register and the Swedish Cause of Death Register. Results: High education level was associated with PD. High IQ was associated with PD (p < 0.0001), both when analyzed as a continuous variable and when divided into three categories. The hazard ratio for the high IQ category compared to the low IQ category was 1.35 (95% confidence interval 1.17–1.55). Strong test results on the subtests, measuring verbal, logic, visuospatial and technical abilities, were also associated with PD. In a subgroup, smoking was inversely associated with PD, as well as with IQ. Conclusions: This study identifies high IQ to be a risk factor for PD. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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). Results The mRS score distributions were better in the above-median s-IGF-I group (>146.7 ng/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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Background: Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy.Methods: This was a registry-based national prospective cohort study with data collected from the Swedish Medical Birth Register, 1982 to 2014, with up to 33 years of follow-up. Included women were of childbearing age (18-45 years) during the initial antenatal visit in their first or second pregnancy (n=1 393 346). We obtained baseline data on body mass index (BMI), smoking, education, and previous disorders. After exclusions, mainly because of previous disorders, the final sample was composed of 1 388 571 women. Cardiomyopathy cases were identified by linking the Medical Birth Register to the National Patient and Cause of Death registers.Results: In total, we identified 1699 cases of cardiomyopathy (mean age at diagnosis, 46.2 [SD 9.1] years) during the follow-up with an incidence rate of 5.9 per 100 000 observation years. Of these, 481 were diagnosed with dilated cardiomyopathy, 246 had hypertrophic cardiomyopathy, 61 had alcohol/drug-induced cardiomyopathy, and 509 had other forms. The lowest risk for being diagnosed with a cardiomyopathy was detected at a BMI of 21 kg/m2, with a gradual increase in risk with higher BMI, particularly for dilated cardiomyopathy, where a hazard ratio of 4.71 (95% CI, 2.81-7.89) was found for severely obese subjects (BMI ≥35 kg/m2), as compared with BMI 20 to <22.5.Conclusions: Elevated BMI among young women was associated with an increased risk of being diagnosed with a subsequent cardiomyopathy, especially dilated cardiomyopathy, starting already at mildly elevated body weight, whereas severe obesity entailed an almost 5-fold increase in risk. With the increasing numbers of persons who are overweight or obese, higher rates of cardiomyopathy can be expected in the future, along with an altered disease burden related to adiposity. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood. Methods: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models. Results: During follow-up (median, 27 years; Q1–Q3, 19–35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5–<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22–1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14–1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06–1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06–1.13) for alcohol/drug-induced cardiomyopathy. Conclusions: Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease. [ABSTRACT FROM AUTHOR]

Aims: 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.Methods and Results: We followed a cohort of Swedish men enrolled in mandatory military conscription in 1968-2005 (n = 1 225 300; mean age 18.3 years) 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 50.1 years). 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).Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Recent research suggests that the prevalence of early heart failure may be on the rise. Compromised mental health in adolescence may help to explain this phenomenon. We aimed to investigate whether nonpsychotic mental disorder and low stress resilience in late adolescence were associated with increased risk of early heart failure. Methods A prospective cohort study of 18-year-old men (n = 1,784,450) who enlisted 1968–2005. At the conscription examination, 74,522 individuals were diagnosed with nonpsychotic mental disorders. Stress resilience was rated by psychologists; values were trichotomized. The risk of heart failure during the 46-year follow-up was calculated with Cox proportional hazards models. Baseline comorbidities, BMI, blood pressure, fitness, IQ, and parental education were included in the models. Results Incident cases of heart failure (n = 9962) were identified in the National Hospital Register. In fully adjusted models, increased risk of early heart failure was observed in males diagnosed with nonpsychotic mental disorders at conscription (hazard ratio (HR), 1.36; 95% confidence interval (CI), 1.25–1.47). The highest risk was seen among men with the risk factor alcohol/substance use (HR 1.90; 95% CI 1.59–2.28). Conscripts with the risk factor low stress resilience showed increased risk of heart failure compared to those with high scores (HR 1.41; 95% CI 1.30–1.53). Conclusion Nonpsychotic mental disorder, as well as low stress resilience in late adolescence may be associated with increased risk of early heart failure. Adolescence is potentially an important time for mental health interventions that may reduce both short and long-term consequences. [ABSTRACT FROM AUTHOR]

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 neuronrelated 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. [ABSTRACT FROM AUTHOR]

An association of higher body mass index (BMI) with lower risk of attempted and completed suicide has been reported. In contrast, increasing BMI has been found to be associated with depression and other risk factors for suicidal behavior. We aimed to investigate this possible paradox in a cohort comprising 49 000 Swedish men. BMI, mental health, lifestyle and socioeconomic measures were recorded at conscription in 1969–70, at ages 18–20. Information on attempted suicide 1973–2008 and completed suicide 1971–2008 was obtained from national records. Hazard ratios (HR) were estimated by Cox proportional hazard models. We found that each standard deviation (SD) increase in BMI was associated with a 12% lower risk of later suicide attempt (HR 0.88, 95% CI 0.83–0.94). Associations were somewhat weaker for completed suicide and did not reach conventional levels of statistical significance (HR 0.93, 95% CI 0.85–1.01). Adjustment for a wide range of possible confounding factors had little effect on the associations. Lower BMI at conscription was also associated with higher prevalence of psychiatric diagnoses, low emotional control and depressed mood. Our results confirm previous findings regarding the association of higher BMI with a reduced risk of suicide, extending them to show similar findings in relation to suicide attempts. The associations were little affected by adjustment for a range of possible confounding factors. However, we found no evidence that high BMI was associated with an increased risk of depression cross-sectionally or longitudinally. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57 kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro. [Copyright &y& Elsevier]

Background: Anxiety 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/design: Using 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. Discussion: Findings 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 registration: The trial was registered at ClinicalTrial.gov NCT03247270 August 8, 2017. [ABSTRACT FROM AUTHOR]

Background: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood.Methods: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models.Results: During follow-up (median, 27 years; Q1-Q3, 19-35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5-<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22-1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14-1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06-1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06-1.13) for alcohol/drug-induced cardiomyopathy.Conclusions: Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease. [ABSTRACT FROM AUTHOR]