Sleep disturbances and cause-specific mortality: Results from the GAZEL cohort study

Poor sleep is an increasing problem in modern society, but most previous studies on the association between sleep and mortality rates have addressed only duration, not quality, of sleep. The authors prospectively examined the effects of sleep disturbances on mortality rates and on important risk factors for mortality, such as body mass index, hypertension, and diabetes. A total of 16,989 participants in the GAZEL cohort study were asked validated questions on sleep disturbances in 1990 and were followed up until 2009, with <1% loss to follow-up. Body mass index, hypertension, and diabetes were measured annually through self-reporting. During follow-up, a total of 1,045 men and women died. Sleep disturbances were associated with a higher overall mortality risk in men (P = 0.005) but not in women (P = 0.33). This effect was most pronounced for men <45 years of age (≥3 symptoms vs. none: hazard ratio = 2.03, 95% confidence interval: 1.24, 3.33). There were no clear associations between sleep disturbances and cardiovascular mortality rates, although men and women with sleep disturbances were more likely to develop hypertension and diabetes (P < 0.001). Compared with people with no sleep disturbances, men who reported ≥3 types of sleep disturbance had an almost 5 times' higher risk of committing suicide (hazard ratio = 4.99, 95% confidence interval: 1.59, 15.7). Future strategies to prevent premature deaths may benefit from assessment of sleep disturbances, especially in younger individuals.     

Cell culture model predicts human disease: Altered expression of junction proteins and matrix metalloproteinases in cervical dysplasia

Background

LAT1/4F2hc heterodimeric complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Although it has been shown that LAT1/4F2hc is highly expressed in a variety of human tumors including gliomas, and LAT1 over-expression is associated with glioma grade and poor prognosis of glioma patients, the precise tissue location of LAT1/4F2hc in gliomas and the precise role of LAT1/4F2hc in glioma biological features remain unclear.

Methods

In the current study, the expressions of LAT1, 4F2hc, CD34 and Ki-67 were investigated by immunohistochemistry in 62 cases of human brain glioma; LAT1/4F2hc expression level, Ki-67 labeling index (Ki-67 LI) and microvessel density (MVD) were measured semi-quantitatively; and the correlation of LAT1/4F2hc expression with histopathological features, Ki-67 LI and MVD in gliomas was further analyzed.

Results

The results showed that both LAT1 and 4F2hc were expressed in all examined specimens. LAT1 but 4F2hc expression levels significantly correlated with the pathological grade and both expression levels significantly correlated with Ki-67 LI of gliomas. We also demonstrated that both LAT1 and 4F2hc immunoreactivity were observed in tumor cells as well as vascular endothelia; furthermore, the LAT1 expression level was markedly associated with glioma MVD as well.

Conclusion

LAT1/4F2hc over-expression is closely correlates with the malignant phenotype and proliferation of gliomas, and LAT1 was associates with glioma angiogenesis. LAT1/4F2hc, especially LAT1, may become a novel potential molecular target for glioma biological therapy.     

Validation of head movement correction and spatiotemporal signal space separation in magnetoencephalography

Objective

Our aim was to assess the effectiveness and reliability of spatiotemporal signal space separation (tSSS) and movement correction (MC) in magnetoencephalography (MEG) recordings disturbed by head movements and magnetized material on the head.

Methods

We recorded MEG from 20 healthy adults in stationary (reference) head position and during controlled head movements. Nearby magnetic interference sources were simulated by attaching magnetized particles on the subject’s head. Auditory and somatosensory stimuli were presented. MC, tSSS and averaging were performed to obtain auditory (AEF) and somatosensory (SEF) evoked fields. Neuronal sources were modeled as equivalent current dipoles. MC was also validated by reconstructing signals generated by current dipoles in a phantom.

Results

After MC, the AEF and SEF responses recorded during intermittent head movements were similar in amplitude to the reference recordings and differed by 5–7 mm in source location. The tSSS method removed artifacts due to the attached magnetized particles but did not affect the reference data.

Conclusions

The methods are able to reliably recover MEG responses contaminated by movements and magnetic artifacts on the head.

Significance

The combination of tSSS and MC methods is especially useful in clinical measurements, where movements and magnetic disturbances are commonly present.     

American heart association’s cardiovascular health metrics and risk of cardiovascular disease mortality among a middle-aged male Scandinavian population

Abstract

Background: The burden of cardiovascular disease (CVD) prompted the American Heart Association to develop a cardiovascular health (CVH) metric as a measure to assess the cardiovascular status of the population. We aimed to assess the association between CVH scores and the risk of CVD mortality among a middle-aged Finnish population.

Methods: We employed the prospective population-based Kuopio Ischemic Heart Disease cohort study comprising of middle-aged men (42–60 years). CVH scores were computed among 2607 participants at baseline and categorized as optimum (0–4), average (5–9), or inadequate (10–14) CVH. Multivariate cox regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) of CVH score for cardiovascular mortality.

Results: During a median follow-up period of 25.8 years, 609 CVD mortality cases were recorded. The risk of CVD mortality increased gradually with increasing CVH score across the range 3–14 (p-value for non-linearity =.77). Men with optimum CVH score had HR (95% CI) for CVD mortality of 0.30 (CI 0.21 – 0.42, p?<?.0001) compared to those with inadequate CVH score after adjustment for conventional cardiovascular risk factors.

Conclusions: CVH score was strongly and continuously associated with the risk of CVD mortality among middle-aged Finnish population and this was independent of other conventional risk factors.

• Key messages

• Achieving optimum cardiovascular health score reduces the risk of cardiovascular mortality.

• Adopting the American Heart Association’s cardiovascular health metrics is a welcome approach for public health awareness and monitoring of cardiovascular health among Scandinavian population.

     

CSF 5-HIAA,cortisol and DHEAS levels in suicide attempters

The serotonin system and the hypothalamic–pituitary–adrenal (HPA) axis are involved in the biological vulnerability to suicidal behaviour. Altered levels of dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS have been reported in neuropsychiatric conditions. The aim of this study was to investigate CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA) and CSF and plasma levels of cortisol and DHEAS in 28 medication free suicide attempters and 19 healthy volunteers. Another aim was to investigate the relationship between neuroendocrine measures and childhood trauma in suicide attempters. As the study design includes a longitudinal part, we investigated whether CSF cortisol, 5-HIAA or DHEAS would predict subsequent suicide. We hypothesized higher cortisol levels in suicide attempters and lower CSF 5-HIAA levels and higher cortisol levels in suicide victims. Suicide attempters had higher CSF and plasma cortisol levels compared to healthy volunteers. Male suicide attempters had higher CSF DHEAS levels and female suicide attempters had lower CSF 5-HIAA levels compared to male and female healthy volunteers respectively. Exposure to interpersonal violence as a child showed a negative correlation with CSF cortisol/DHEAS ratio adjusted for age, gender and depression severity in a regression analysis. Suicide victims tended to have low CSF 5-HIAA and high CSF cortisol. Abused suicide victims had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. The results underlie the important role of the serotonergic system and HPA axis in suicidal behaviour and suggest that CSF DHEAS may be elevated in male suicide attempters.     

Enhanced early-latency electromagnetic activity in the left premotor cortex is associated with successful phonetic categorization

Sensory-motor interactions between auditory and articulatory representations in the dorsal auditory processing stream are suggested to contribute to speech perception, especially when bottom-up information alone is insufficient for purely auditory perceptual mechanisms to succeed. Here, we hypothesized that the dorsal stream responds more vigorously to auditory syllables when one is engaged in a phonetic identification/repetition task subsequent to perception compared to passive listening, and that this effect is further augmented when the syllables are embedded in noise. To this end, we recorded magnetoencephalography while twenty subjects listened to speech syllables, with and without noise masking, in four conditions: passive perception; overt repetition; covert repetition; and overt imitation. Compared to passive listening, left-hemispheric N100m equivalent current dipole responses were amplified and shifted posteriorly when perception was followed by covert repetition task. Cortically constrained minimum-norm estimates showed amplified left supramarginal and angylar gyri responses in the covert repetition condition at ~100ms from stimulus onset. Longer-latency responses at ~200ms were amplified in the covert repetition condition in the left angular gyrus and in all three active conditions in the left premotor cortex, with further enhancements when the syllables were embedded in noise. Phonetic categorization accuracy and magnitude of voice pitch change between overt repetition and imitation conditions correlated with left premotor cortex responses at ~100 and ~200ms, respectively. Together, these results suggest that the dorsal stream involvement in speech perception is dependent on perceptual task demands and that phonetic categorization performance is influenced by the left premotor cortex.     

Natural coniferous resin salve used to treat complicated surgical wounds: pilot clinical trial on healing and costs

Resin is a natural product of coniferous trees. Salves manufactured from spruce resin (Picea abies) have been used for centuries to treat wounds and skin infections. We report a pilot clinical trial designed to investigate healing rates, factors that contribute to delayed wound healing, cost‐effectiveness, and incidence of allergic reactions when resin salve is used to treat complicated surgical wounds. The trial involved 23 patients in whom wound healing after surgery was delayed. These patients were assigned to resin salve treatment. The primary outcome measure was the number of days to complete wound healing. Secondary objectives included an assessment of factors contributing to delayed wound healing, an estimation of associated costs, and an investigation into the occurrence of allergic reactions related to resin salve therapy. The study achieved a healing rate of 100%. The mean ± SD healing time was 43 ± 24 days. The mean ± SD wound size (length × width × depth) was (29 ± 19) × (12 ± 7) × (4 ± 3) mm. Wound size, use of corticosteroids or other immunosuppressants, and immobilization were statistically significant (P < 0.05) contributors to delayed wound healing and impaired re‐epithelialization. The total mean ± SD costs of the resin salve treatment were €45.0 ± 26.0 per patient during the entire treatment period and €1.2 ± 0.5 per treatment day. The rate of allergic reactions was 0%. The results of this pilot trial indicate that complicated surgical wounds may be treated successfully with resin salve. The treatment method is clinically effective and cost‐effective, and the rate of allergic reactions is low.     

Association between folate intake and melancholic depressive symptoms. A Finnish population-based study

BackgroundAn association between low blood folate levels and depressive symptoms (DS) has been reported in several epidemiological studies, but no studies have examined folate intake in melancholic or non-melancholic DS in population-based samples.MethodsThe aim of the study was to evaluate folate intake in DS with or without melancholic characteristics as a part of the Finnish diabetes prevention program (FIN-D2D). Altogether, 4500 randomly selected subjects aged 45–74 years were selected from the National Population Register. The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out in 2007 according to the WHO MONICA project. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off ≥ 10 points). A summary score of melancholic items in the BDI was used in dividing the participants with DS (N = 429) into melancholic (N = 138) and non-melancholic DS (N = 291) subgroups. Folate intake was assessed using a validated food frequency questionnaire (FFQ).ResultsDS associated linearly with gender specific tertiles of folate intake (p for linearity = 0.003). The OR for melancholic DS was 0.55 (95%CI 0.34 to 0.90) for the high tertile of folate intake versus the low (p for linearity = 0.018), while the ORs for non-melancholic DS were nonsignificant.LimitationsAssessment of DS was based on a self-rating scale, and the population was in advanced middle-aged.ConclusionsA low folate intake was associated with DS through its effect on melancholic DS.