Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases

Background Resting heart rate (HR) and its variability (HRV) reflects the cardiac sympathovagal balance that is stimulated by head-up tilting. HRV is influenced by the level of HR, but how much HRV offers additional information about cardiac autonomic tone than HR alone remains unresolved. We examined the relation of resting HR with HRV during head-up tilt. Methods. Hemodynamics of 569 subjects without known cardiovascular diseases and medications with direct cardiovascular effects were recorded using whole-body impedance cardiography, radial pulse wave analysis, and electrocardiography-based HRV analysis during passive head-up tilt. Results. Higher low frequency to the high-frequency ratio (LF/HF) of HRV (reflecting sympathovagal balance) was associated with higher HR in supine (p < .05, both linear regression analysis and variance analysis comparing HR tertiles) and upright postures (p < .001, linear regression analysis). The association of HR with HRV during tilt-testing remained significant when the HR dependence of HRV was mathematically weakened by dividing the HRV power spectra with the fourth power of the average RR-interval. Conclusion. Higher resting HR is related to higher LF/HF both supine and upright, reflecting elevated sympathetic influence on cardiac autonomic modulation. Lower resting HR is associated with lower resting LF/HF, while the differences in LF/HF between the HR tertiles were minor during head-up tilt, suggesting a greater change in cardiac sympathovagal balance in response to upright posture in those with lowest resting HR. Altogether, resting HR well predicts HRV levels during head-up tilt.Trial registration: Clinicaltrialsregister.eu 2006-002065-39, first registered 5 May 2006. ClinicalTrials.gov NCT01742702, first registered 5 December 2012.publishedVersionPeer reviewe

Intravenously Administered Alphavirus Vector VA7 Eradicates Orthotopic Human Glioma Xenografts in Nude Mice

VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma.In vitro, U87, U251, and A172 human glioma cells were infected and killed by VA7-EGFP. In vivo, antiglioma activity of VA7 was tested in Balb/c nude mice using U87 cells stably expressing firefly luciferase in subcutaneous and orthotopic tumor models. Intravenously administered VA7-EGFP completely eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors. A single intravenous injection of either VA7-EGFP or VA7 expressing Renilla luciferase (VA7-Rluc) into mice bearing orthotopic U87Fluc tumors caused a complete quenching of intracranial firefly bioluminescence and long-term survival in total 16 of 17 animals. In tumor-bearing mice injected with VA7-Rluc, transient intracranial and peripheral Renilla bioluminescence was observed. Virus was well tolerated and no damage to heart, liver, spleen, or brain was observed upon pathological assessment at three and ninety days post injection, despite detectable virus titers in these organs during the earlier time point.VA7 vector is apathogenic and can enter and destroy brain tumors in nude mice when administered systemically. This study warrants further elucidation of the mechanism of tumor destruction and attenuation of the VA7 virus

Dispositional optimism and pessimism in association with cognitive abilities in early and middle adulthood

Abstract The aim of the current study was to examine the associations of dispositional optimism and pessimism with cognitive abilities in adulthood. We performed two studies with data sets from the prospective Northern Finland Birth Cohort Studies: 26-year-olds (N = 383) and 46-year-olds (N = 5042). In both samples, dispositional optimism and pessimism were measured with Carver and Scheier’s Life Orientation Test -Revised. In the data of 26-year-olds, the cognitive abilities assessed were reasoning, vocabulary, verbal fluency, fine-motor skills, selective attention, impulse control, and memory, while in 46-year-olds, memory was assessed. The analyses were carried out using multiple linear regression, and the associations were adjusted for gender, educational level, mother’s educational level, and depression. Our results indicated that (I.) higher dispositional optimism and lower pessimism were associated with higher reasoning skills in young adults, and (II.) higher pessimism was related to lower scores on memory test in middle-aged adults. The findings provide a closer look on how dispositional optimism and pessimism are associated with the core cognitive abilities in adults

Military performance of men with attention-deficit/hyperactivity disorder:findings from a follow-up study in the Northern Finland birth cohort 1986

Abstract Purpose: The aim of this study was to assess the military performance of men with adolescent attention-deficit/hyperactivity disorder (ADHD) and men with childhood ADHD (in remission during adolescence) as compared with controls without ADHD. Methods: The study employs the general population-based Northern Finland Birth Cohort 1986 (NFBC1986) together with data received from the Finnish Defence Forces (FDF). A total of 38 men with childhood ADHD and 67 with adolescent ADHD were compared with 160 controls. Results: The men with adolescent ADHD were more often deemed unfit for military service, had more military health care visits, more often committed at least one offence during service, received poorer evaluations for team leadership skills and indulged in more alcohol consumption and smoking than the controls, while those with childhood ADHD did not differ from the controls in their military fitness, but received poorer evaluations for team leadership skills and smoked more than did the controls. Conclusions: The conscripts with adolescent ADHD performed worse on many military parameters, but the men with ADHD in remission did not seem to suffer from such negative effects on military performance. The childhood ADHD group in particular was nevertheless somewhat limited in size, which might have led to a Type II error

Antisocial and borderline personality disorders in the offspring of antenatally depressed mothers:a follow-up until mid-adulthood in the Northern Finland 1966 birth cohort

Abstract Background: Maternal depression is common during pregnancy, affecting 10–15% of mothers. In previous reports, the offspring of antenatally depressed mothers have had an elevated risk for antisocial, criminal and violent behaviour in adolescence, and for borderline personality features in childhood, but long-term outcomes are unknown. Aims: To study whether the adult offspring of antenatally depressed mothers have an elevated risk for antisocial (ASPD) or borderline personality disorder (BPD) when followed until mid-adulthood. Methods: In the general population-based Northern Finland 1966 Birth Cohort, mothers of 12,058 children were asked during mid-gestation if they felt depressed. Of the mothers, 14% reported being depressed. The offspring were followed for 49 years. The diagnoses of in- and outpatient-treated ASPD and BPD in the offspring were detected using the Finnish Care Register for Healthcare. Maternal antenatal smoking, newborn´s low birthweight or short gestational age, father’s social class, and family type at birth were considered as confounding variables. Logistic regression analyses on the potential confounders were performed. Maternal postnatal depression and paternal ASPD information was not available. Results: In the male offspring of antenatally depressed mothers, the risk for ASPD was elevated (adjusted odds ratio 5.6; 95% confidence interval 1.8–17.8), but not in female offspring. The risk for BPD was not elevated in the offspring of antenatally depressed mothers in this study. Conclusions: The sons of antenatally depressed mothers had an increased risk for ASPD. Prevention and treatment of antenatal depression might present an opportunity to decrease the risk of antisocial personality in the offspring

Individual changes of central blood pressure in response to upright posture : different hemodynamic phenotypes

OBJECTIVES: Most studies about upright regulation of blood pressure have focused on orthostatic hypotension despite the diverse hemodynamic changes induced by orthostatic challenge. We investigated the effect of passive head-up tilt on aortic blood pressure. METHODS: Noninvasive peripheral and central hemodynamics in 613 volunteers without cardiovascular morbidities or medications were examined using pulse wave analysis, whole-body impedance cardiography and heart rate variability analysis. RESULTS: In all participants, mean aortic SBP decreased by -4 (-5 to -3) mmHg [mean (95% confidence intervals)] and DBP increased by 6 (5--6) mmHg in response to upright posture. When divided into tertiles according to the supine-to-upright change in aortic SBP, two tertiles presented with a decrease [-15 (-14 to -16) and -4 (-3 to -4) mmHg, respectively] whereas one tertile presented with an increase [+7 (7-- 8) mmHg] in aortic SBP. There were no major differences in demographic characteristics between the tertiles. In regression analysis, the strongest explanatory factors for upright changes in aortic SBP were the supine values of, and upright changes in systemic vascular resistance and cardiac output, and supine aortic SBP. CONCLUSION: In participants without cardiovascular disease, the changes in central SBP during orthostatic challenge are not uniform. One-third presented with higher upright than supine aortic SBP with underlying differences in the regulation of systemic vascular resistance and cardiac output. These findings emphasize that resting blood pressure measurements give only limited information about the blood pressure status.publishedVersionPeer reviewe

Frequent intoxication and alcohol tolerance in adolescence:associations with psychiatric disorders in young adulthood

Abstract Aims: To assess the associations of intoxication frequency and number of drinks needed to become intoxicated in mid‐adolescence with onset of psychiatric disorders in early adulthood. Design, Setting and Participants: Prospective cohort study in Northern Finland, with people from the Northern Finland Birth Cohort 1986 who self‐reported adolescent alcohol use: 6548 subjects (69.4% of the original sample). Data on alcohol use were collected using questionnaires at ages 15–16 years. Measurements: Outcomes were any non‐organic psychosis, mood disorder, anxiety disorder, any substance use disorder (SUD) and all the studied psychiatric disorders in early adulthood gathered from nation‐wide health care, pension and insurance registers. Number of drinks needed to become intoxicated was categorized into three classes: (1) no alcohol use or intoxication, and (2) low and (3) high alcohol tolerance (more than seven/nine drinks for females/males) groups. Similarly, intoxication frequency was divided into three classes: (1) never, (2) one to two times and (3) three or more times during the past 30 days. Information regarding gender, family type, other drug use, psychopathology using Youth Self‐Report (YSR) total score and parental psychiatric disorders were used as covariates. Findings: In the multivariable analyses, both low [odds ratio (OR) = 3.0, 95% confidence interval (CI) = 1.3–6.7, P‐value = 0.009] and high (OR = 4.4, 95% CI = 1.8–11.1, P‐value = 0.001) alcohol tolerance were associated with increased risk of SUD. More frequent intoxication was associated with increased frequency of SUD (OR = 3.9, 95% CI = 2.0–7.3, P‐value &lt; 0.001) and mood disorder (OR = 1.6, 95% CI = 1.1–2.3, P‐value = 0.008). The latter was attenuated after adjusting with concurrent psychopathology (YSR) and other drug use. Conclusions: Both higher alcohol tolerance and frequent intoxication in adolescence appear to be associated with increased risk of future substance use disorder