Social Mobility and Health-Related Quality of Life Trajectory Classes Among Older Women and Men.

OBJECTIVES: Changes in socioeconomic status (SES) during life may impact health in old age. We investigated whether social mobility and childhood and adulthood SES are associated with trajectories of health-related quality of life (HrQoL) over a 17-year period. METHODS: We used data from the Helsinki Birth Cohort Study (n = 2003, 46% men, mean age 61.5 years). Social mobility was derived from childhood SES, obtained from healthcare records, and register-based adulthood SES. RESULTS: Logistic regression models showed that lower adulthood SES was associated with lower physical HrQoL trajectories. Among men low (OR 3.95, p < .001), middle (OR 2.20, p = .006), and declining lifetime SES (OR 2.41, p = .001) were associated with lower physical HrQoL trajectories compared to men with high SES. Socioeconomic status was not associated with mental HrQoL trajectories. DISCUSSION: Declining SES during life course may have negative health consequences, while improving SES is potentially as beneficial as high SES to later-life health among men.

Active Aging in Senior Housing Residents and Community-Dwelling Older Adults: A Comparative Study in Finland.

OBJECTIVES: Leading an active life in old age underpins positive life experience. This study aimed to compare the levels of active aging in senior housing residents and community-dwelling older people. METHODS: We combined data from the BoAktiv senior house survey (N = 336, 69% women, mean age 83 years) and AGNES cohort study among community-dwelling older adults (N = 1021, 57% women, mean age 79 years). Active aging was assessed with the University of Jyvaskyla Active Aging scale. Data were analyzed with general linear models, and the analyses were stratified by sex. RESULTS: Men in senior houses demonstrated lower active aging scores in general than community-dwelling men. Women in senior houses showed greater will to be active, but poorer ability and possibilities for activity than community-dwelling women. DISCUSSION: Despite the social and supporting environment, senior housing residents' possibilities for leading an active life seem to be compromised, potentially leading to an unmet activity need.

Mental, Physical and Social Functioning in Independently Living Senior House Residents and Community-Dwelling Older Adults.

Senior houses provide social interaction and support, potentially supporting older people's physical and mental functioning. Few studies have investigated functioning of senior house residents. The aim was to compare functioning between senior house residents and community-dwelling older adults in Finland. We compared senior house residents (n = 336, 69% women, mean age 83 years) to community-dwelling older adults (n = 1139, 56% women, mean age 74 years). Physical and mental functioning were assessed using the SF 36-Item Health Survey. Loneliness and frequency of social contacts were self-reported. The analyses were adjusted for age, socioeconomic factors and diseases. Physical functioning was lower among men in senior houses compared to community-dwelling men (mean 41.1 vs. 46.4, p = 0.003). Mental functioning or the frequency of social contacts did not differ between type of residence in either sex. Loneliness was higher among women in senior houses compared to community-dwelling women (OR = 1.67, p = 0.027). This was not observed in men. Results suggest that women in senior houses had similar physical and mental functioning compared to community-dwelling women. Male senior house residents had poorer physical functioning compared to community-dwelling men. Women living in senior houses were lonelier than community-dwelling women despite the social environment.

Long-term survival after primary intracerebral hemorrhage: A population-based case-control study spanning a quarter of a century.

BACKGROUND AND PURPOSE: The aim of this study was to determine the differences in life expectancy and causes of death after primary intracerebral hemorrhage (ICH) relative to general population controls. METHODS: In a population-based setting, 963 patients from Northern Ostrobothnia who had their first-ever ICH between 1993 and 2008 were compared with a cohort of 2884 sex- and age-matched controls in terms of dates and causes of death as extracted from the Causes of Death Register kept by Statistics Finland and valid up to the end of 2017. RESULTS: Of our 963 patients, 781 died during the follow-up time (mortality 81.1%). Cerebrovascular disease was the most common cause of death for these patients, 37.3% compared with 8.2% amongst the controls. The most common reasons for cerebrovascular mortality in the ICH patients were late sequelae of ICH in 12.8% (controls 0%) and new bleeding in 10.6% (controls 1.0%). The long-term survivors had a smaller ICH volume (median 12 ml) than those patients who died within 3 months (median 39 ml). The mortality rate of ICH patients during a follow-up between 12 and 24 years was still higher than that of their controls (hazard ratio 2.08, 95% confidence interval 1.58-2.74, p < 0.001). CONCLUSIONS: Very long-term ICH survivors have a constant excess mortality relative to controls even 10 years after the index event. A significantly larger proportion of patients died of cerebrovascular causes and fewer because of cancer relative to the controls.

Increased mortality after post-stroke epilepsy following primary intracerebral hemorrhage.

OBJECTIVES: This study aimed to determine whether post-stroke epilepsy (PSE) predicts mortality, and to describe the most prominent causes of death (COD) in a long-term follow-up after primary intracerebral hemorrhage (ICH). METHODS: We followed 3-month survivors of a population-based cohort of primary ICH patients in Northern Ostrobothnia, Finland, for a median of 8.8 years. Mortality and CODs were compared between those who developed PSE and those who did not. PSE was defined according to the ILAE guidelines. CODs were extracted from death certificates (Statistics Finland). RESULTS: Of 961 patients, 611 survived for 3 months. 409 (66.9%) had died by the end of the follow-up. Pneumonia was the only COD that was significantly more common among the patients with PSE (56% vs. 37% of deaths). In the multivariable models, PSE (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.06-1.87), age (HR 1.07, 95% CI 1.06-1.08), male sex (HR 1.35, 95% CI 1.09-1.67), dependency at 3 months (HR 1.52, 95% CI 1.24-1.88), non-subcortical ICH location (subcortical location HR 0.78, 95% CI 0.61-0.99), diabetes (HR 1.43, 95% CI 1.07-1.90) and cancer (HR 1.45, 95% CI 1.06-1.98) predicted death in the long-term follow-up. CONCLUSION: PSE independently predicted higher late morality of ICH in our cohort. Pneumonia-related deaths were more common among the patients with PSE.

Empowerment-enabling home and school environments and self-rated health among Finnish adolescents.

Perceived health during adolescence has not only immediate consequences for individuals and for society, but also long-term. We need to understand better the health development in this period of the lifespan. Empowerment may be one pathway through which social factors and conditions translate into health effects. This study aimed to examine whether empowerment-enabling home and school environments are associated with self-rated health among adolescents, and whether the associations differ between genders, age or majority/minority language groups. Anonymous questionnaire data from respondents aged 11, 13 and 15 years were obtained from the Health Behaviour in School-aged Children study, conducted in Finland in 2014 in Finnish- and Swedish-speaking schools (n = 5925/1877). The proportion rating their health as excellent varied between 33.6 (11-year-olds) and 23.1% (15-year-olds), boys rating their health as excellent more often than girls in all age groups. Findings showed that indicators of both empowerment-enabling home and school environments were independently and positively related to adolescents' self-rated health. Whereas a respectful, accepting, kind and helpful attitude among classmates and a good home atmosphere were quite consistently associated with excellent health, there were gender and age differences with concern to the other empowerment-enabling indicators. Moreover, there were gender-, age- and language-related differences regarding adolescents' perceptions of how empowerment enabling their environments were. Home and school environments that create opportunities through encouragement and care, and through strengthening feelings of being secure, accepted and respected are potentially empowerment enabling. This study suggests that such environmental qualities are important for the perceived health of young people.

Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage.

OBJECTIVE: To identify the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. METHODS: We performed a retrospective study of patients who had had their first-ever PICH between January 1993 and January 2008 in Northern Ostrobothnia, Finland, and who survived for at least 3 months. These patients were followed up for PSE. The associations between PSE occurrence and sex, age, Glasgow Coma Scale (GCS) score on admission, hematoma location and volume, early seizures, and other possible risk factors for PSE were assessed using the Cox proportional hazards regression model. RESULTS: Of the 615 PICH patients who survived for longer than 3 months, 83 (13.5%) developed PSE. The risk of new-onset PSE was highest during the first year after PICH with cumulative incidence of 6.8%. In univariable analysis, the risk factors for PSE were early seizures, subcortical hematoma location, larger hematoma volume, hematoma evacuation, and a lower GCS score on admission, whereas patients with infratentorial hematoma location or hypertension were less likely to develop PSE (all variables p < 0.05). In multivariable analysis, we found subcortical location (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.35-3.81, p < 0.01) and early seizures (HR 3.63, 95% CI 1.99-6.64, p < 0.01) to be independent risk factors, but patients with hypertension had a lower risk of PSE (HR 0.54, 0.35-0.84, p < 0.01). CONCLUSIONS: Subcortical hematoma location and early seizures increased the risk of PSE after PICH in long-term survivors, while hypertension seemed to reduce the risk.

Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early and delayed afterdepolarizations.

BACKGROUND: Induced pluripotent stem cells (iPSC) provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly caused by mutations in the cardiac ryanodine receptor (RyR2). In this study the cellular characteristics of CPVT are investigated and whether the electrophysiological features of this mutation can be mimicked using iPSC -derived cardiomyocytes (CM). METHODOLOGY/PRINCIPAL FINDINGS: Spontaneously beating CMs were differentiated from iPSCs derived from a CPVT patient carrying a P2328S mutation in RyR2 and from two healthy controls. Calcium (Ca(2+)) cycling and electrophysiological properties were studied by Ca(2+) imaging and patch-clamp techniques. Monophasic action potential (MAP) recordings and 24h-ECGs of CPVT-P2328S patients were analyzed for the presence of afterdepolarizations. We found defects in Ca(2+) cycling and electrophysiology in CPVT CMs, reflecting the cardiac phenotype observed in the patients. Catecholaminergic stress led to abnormal Ca(2+) signaling and induced arrhythmias in CPVT CMs. CPVT CMs also displayed reduced sarcoplasmic reticulum (SR) Ca(2+) content, indicating leakage of Ca(2+) from the SR. Patch-clamp recordings of CPVT CMs revealed both delayed afterdepolarizations (DADs) during spontaneous beating and in response to adrenaline and also early afterdepolarizations (EADs) during spontaneous beating, recapitulating the changes seen in MAP and 24h-ECG recordings of patients carrying the same mutation. CONCLUSIONS/SIGNIFICANCE: This cell model shows aberrant Ca(2+) cycling characteristic of CPVT and in addition to DADs it displays EADs. This cell model for CPVT provides a platform to study basic pathology, to screen drugs, and to optimize drug therapy.

Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture.

Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and is associated with prolonged cardiac repolarization time and increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) and drug-induced LQTS both result from altered function of the hERG channel. We investigated whether the electrophysiological characteristics of LQT2 can be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology. Spontaneously beating cardiomyocytes were differentiated from two iPSC lines derived from an individual with LQT2 carrying the R176W mutation in the KCNH2 (HERG) gene. The individual had been asymptomatic except for occasional palpitations, but his sister and father had died suddenly at an early age. Electrophysiological properties of LQT2-specific cardiomyocytes were studied using microelectrode array and patch-clamp, and were compared with those of cardiomyocytes derived from control cells. The action potential duration of LQT2-specific cardiomyocytes was significantly longer than that of control cardiomyocytes, and the rapid delayed potassium channel (I(Kr)) density of the LQT2 cardiomyocytes was significantly reduced. Additionally, LQT2-derived cardiac cells were more sensitive than controls to potentially arrhythmogenic drugs, including sotalol, and demonstrated arrhythmogenic electrical activity. Consistent with clinical observations, the LQT2 cardiomyocytes demonstrated a more pronounced inverse correlation between the beating rate and repolarization time compared with control cells. Prolonged action potential is present in LQT2-specific cardiomyocytes derived from a mutation carrier and arrhythmias can be triggered by a commonly used drug. Thus, the iPSC-derived, disease-specific cardiomyocytes could serve as an important platform to study pathophysiological mechanisms and drug sensitivity in LQT2.

Stressor-dependent regulation of the heat shock response in zebrafish, Danio rerio.

Heat shock transcription factors (HSFs) regulate expression of heat shock proteins (Hsps). We have previously shown that in zebrafish a unique isoform, zHSF1b, disappears concomitant with heat shock-induced Hsp70 expression. To characterize the role of zHSF1a and zHSF1b isoforms in the regulation of the stress response in vivo, we have carried out cadmium (10-100 microM) and copper (10-30 microM) exposures in order to specify whether the disappearance of HSF1b is specific for heat stress. After 4-h metal exposures we analyzed the expression of hsp70, zHSF1a, zHSF1b and metallothionein (MT) by reverse transcriptase polymerase chain reaction in zebrafish liver, gonads and gills. Although cadmium is a known inducer of Hsps, it did not affect hsp70 expression significantly in the studied tissues. Induction of hsp70 was observed upon copper exposure in liver and gonads, but not in gills. Neither metal affected the zHSF1a/b ratio. Both cadmium and copper exposure caused upregulation of MT, regulator of metal homeostasis and detoxification, confirming that the tissues were subjected to metal loads. Thus, hsp70 appears to be more weakly induced upon metal exposure than in response to heat shock and HSF1 isoforms may participate in stressor-specific regulation of hsp70.

Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB.

Nef and Vpr are lentiviral accessory proteins that have been implicated in regulation of cellular gene expression. We noticed that Vpr can potentiate Nef-induced activation of nuclear factor of activated T cells (NFAT)-dependent transcription. Unlike Nef, which stimulated calcium signaling to activate NFAT, Vpr functioned farther downstream. Similar to the positive effects of Vpr on most of the transcriptional test systems that we used, potentiation of NFAT-directed gene expression was relatively modest in magnitude (two- to threefold) and depended on the cell cycle-arresting capacity of Vpr. By contrast, we found that Vpr could cause more than fivefold upregulation of cyclic AMP response element (CRE)-directed transcription via a mechanism that did not require Vpr-induced G2/M arrest. This effect, however, was only evident under suboptimal conditions known to lead to serine phosphorylation of the CRE binding factor (CREB) but not to CREB-dependent gene expression. This suggested that Vpr may act by stabilizing interactions with CREB and its transcriptional cofactor CREB binding protein (CBP). Indeed, this effect could be blocked by cotransfection of the adenoviral CBP inhibitor E1A. These results provide additional evidence for cell cycle-independent regulation of gene expression by Vpr and implicate CREB as a potentially important target for Vpr action in HIV-infected host cells.