Relationship between inflammation and cognitive function in obstructive sleep apnea

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.

Assessing vegetation cover and biomass in restored erosion areas in Iceland using SPOT satellite data

Due to highly erodible volcanic soils and a harsh climate, livestock grazing in Iceland has led to serious soil erosion on about 40% of the country's surface. Over the last 100 years, various revegetation and restoration measures were taken on large areas distributed all over Iceland in an attempt to counteract this problem. The present research aimed to develop models for estimating percent vegetation cover (VC) and aboveground biomass (AGB) based on satellite data, as this would make it possible to assess and monitor the effectiveness of restoration measures over large areas at a fairly low cost. Models were developed based on 203 vegetation cover samples and 114 aboveground biomass samples distributed over five SPOT satellite datasets. All satellite datasets were atmospherically corrected, and digital numbers were converted into ground reflectance. Then a selection of vegetation indices (VIs) was calculated, followed by simple and multiple linear regression analysis of the relations between the field data and the calculated VIs. Best results were achieved using multiple linear regression models for both %VC and AGB. The model calibration and validation results showed that R2 and RMSE values for most VIs do not vary very much. For percent VC, R2 values range between 0.789 and 0.822, leading to RMSEs ranging between 15.89% and 16.72%. For AGB, R2 values for low-biomass areas (AGB < 800 g/m2) range between 0.607 and 0.650, leading to RMSEs ranging between 126.08 g/m2 and 136.38 g/m2. The AGB model developed for all areas, including those with high biomass coverage (AGB > 800 g/m2), achieved R2 values between 0.487 and 0.510, resulting in RMSEs ranging from 234 g/m2 to 259.20 g/m2. The models predicting percent VC generally overestimate observed low percent VC and slightly underestimate observed high percent VC. The estimation models for AGB behave in a similar way, but over- and underestimation are much more pronounced. These results show that it is possible to estimate percent VC with high accuracy based on various VIs derived from SPOT satellite data. AGB of restoration areas with low-biomass values of up to 800 g/m2 can likewise be estimated with high accuracy based on various VIs derived from SPOT satellite data, whereas in the case of high biomass coverage, estimation accuracy decreases with increasing biomass values. Accordingly, percent VC can be estimated with high accuracy anywhere in Iceland, whereas AGB is much more difficult to estimate, particularly for areas with high-AGB variability.

Learning to drive: learners' self-reported cognitive failure level predicts driving instructor's observation rating of driving performance

OBJECTIVES Evidence increases that cognitive failure may be used to screen for drivers at risk. Until now, most studies have relied on driving learners. This exploratory pilot study examines self-report of cognitive failure in driving beginners and error during real driving as observed by driving instructors. METHODS Forty-two driving learners of 14 driving instructors filled out a work-related cognitive failure questionnaire. Driving instructors observed driving errors during the next driving lesson. In multiple linear regression analysis, driving errors were regressed on cognitive failure with the number of driving lessons as an estimator of driving experience controlled. RESULTS Higher cognitive failure predicted more driving errors (p < .01) when age, gender and driving experience were controlled in analysis. CONCLUSIONS Cognitive failure was significantly associated with observed driving errors. Systematic research on cognitive failure in driving beginners is recommended.

Effects of weight on blood pressure at rest and during exercise.

Body weight (BW) and blood pressure (BP) have a close relationship, which has been accounted for by hormonal changes. No previous study has evaluated the effect of wearing an external weight vest on BP to determine whether there is a simple mechanism between BW and BP. Seventeen healthy volunteers underwent weight reduction (WR) through caloric restriction. Before and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before and after WR, exercise testing was performed twice with the random allocation of a weight vest (10 kg) during one of the tests. Linear regression was used to detect independent associations between BP and the weight vest, BW and body fat percentage. BW decreased from 89.4 ± 15.4 kg to 79.1 ± 14.0 kg following WR (P<0.001). WR led to significant decreases in BP at rest (from 130.0/85.9 mm Hg to 112.5/77.8 mm Hg, P<0.001 for systolic and diastolic BPs) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7 mm Hg before and 125.8/84.6 mm Hg after WR) and during exercise. Linear regression analysis identified an independent association between the weight vest and BP (P=0.006 for systolic BP and P=0.009 for diastolic BP at rest). This study demonstrates that wearing an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat. More research is needed to understand the physiological mechanisms between weight and BP.

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

Quantification of pleural effusion from single area measurements on CT

The objective of this study was to determine if area measurements of pleural fluid on computed tomography (CT) reflect the actual pleural fluid volume (PEvol) as measured at autopsy, to establish a formula to estimate the volume of pleural effusion (PEest), and to test the accuracy and observer reliability of PEest.132 human cadavers, with pleural effusion were divided into phase 1 (n = 32) and phase 2 (n = 100). In phase 1, PEvol was compared to area measurements on axial (axA), sagittal (sagA), and coronal (corA) CT images. Linear regression analysis was used to create a formula to calculate PEest. In phase 2, intra-class correlation (ICC) was used to assess inter-reader reliability and determine the agreement between PEest and PEvol. PEvol correlated to a higher degree to axA (r s mean = 0.738; p < 0.001) than to sagA (r s mean = 0.679, p < 0.001) and corA (r s mean = 0.709; p < 0.001). PEest can be established with the following formula: axA × 0.1 = PEest. Mean difference between PEest and PEvol was less than 40 mL (ICC = 0.837-0.874; p < 0.001). Inter-reader reliability was higher between two experienced readers (ICC = 0.984-0.987; p < 0.001) than between an inexperienced reader and both experienced readers (ICC = 0.660-0.698; p < 0.001). Pleural effusions may be quantified in a rapid, reliable, and reasonably accurate fashion using single area measurements on CT.

Estimation of heart weight by post-mortem cardiac magnetic resonance imaging

Introduction The aim of this study was to determine which single measurement on post-mortem cardiac MR reflects actual heart weight as measured at autopsy, assess the intra- and inter-observer reliability of MR measurements, derive a formula to predict heart weight from MR measurements and test the accuracy of the formula to prospectively predict heart weight. Materials and methods 53 human cadavers underwent post-mortem cardiac MR and forensic autopsy. In Phase 1, left ventricular area and wall thickness were measured on short axis and four chamber view images of 29 cases. All measurements were correlated to heart weight at autopsy using linear regression analysis. In Phase 2, single left ventricular area measurements on four chamber view images (LVA_4C) from 24 cases were used to predict heart weight at autopsy based on equations derived during Phase 1. Intra-class correlation coefficient (ICC) was used to determine inter- and intra-reader agreement. Results Heart weight strongly correlates with LVA_4C (r=0.78 M; p<0.001). Intra-reader and inter-reader reliability was excellent for LVA_4C (ICC=0.81–0.91; p<0.001 and ICC=0.90; p<0.001 respectively). A simplified formula for heart weight ([g]≈LVA_4C [mm2]×0.11) was derived based on linear regression analysis. Conclusions This study shows that single circumferential area measurements of the left ventricle in the four chamber view on post-mortem cardiac MR reflect actual heart weight as measured at autopsy. These measurements yield an excellent intra- and inter-reader reliability and can be used to predict heart weight prior to autopsy or to give a reasonable estimate of heart weight in cases where autopsy is not performed.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.

Respiratory-related leg movements and their relationship with periodic leg movements during sleep

STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity. MEASUREMENTS AND RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM. CONCLUSION: The time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.

Psychometric and biohormonal indices of dental anxiety in children. A prospective cohort study.

The stress of dental treatment often elicits negative emotions in children, expressed as dental fear or anxiety. Highly anxious children obstruct treatment and avoid therapy, further amplifying oral health problems. The aim of this study was to examine the neuroendocrine and autonomic nervous system responses to dental treatment and their possible interactions and associations with psychometric indices of anxiety, caries, previous dental experience, anesthesia, age and gender in school children. Upon informed consent, saliva was obtained from 97 children (59% males, mean age ±  SD: 89.73 ± 15 months) in the Clinic of pediatric dentistry before treatment, immediately post-treatment and at the recall visit to determine cortisol and salivary alpha-amylase (sAA) levels. Dental and general anxiety was assessed through specific questionnaires completed by the children. Compared to pre-treatment, cortisol levels were increased following treatment, while sAA levels were higher at the recall. Pre- and post-treatment cortisol and sAA responses were positively correlated. Dental and general anxiety questionnaire scores were also significantly correlated with each other. The integrated autonomic and neuroendocrine responses prior to treatment were correlated with state anxiety and those following treatment with dental anxiety. However, univariable and multivariable linear regression analysis associated post-treatment cortisol, but not sAA, levels with dental anxiety. No associations of cortisol or sAA responses with caries, age, gender, previous dental experience or anesthesia were detected. These data provide some evidence that both sAA and cortisol levels are altered in children in anticipation or during dental treatment, but only cortisol levels are associated to dental anxiety.

Contrasting interannual and multidecadal NAO variability

Decadal and longer timescale variability in the winter North Atlantic Oscillation (NAO) has considerable impact on regional climate, yet it remains unclear what fraction of this variability is potentially predictable. This study takes a new approach to this question by demonstrating clear physical differences between NAO variability on interannual-decadal (<30 year) and multidecadal (>30 year) timescales. It is shown that on the shorter timescale the NAO is dominated by variations in the latitude of the North Atlantic jet and storm track, whereas on the longer timescale it represents changes in their strength instead. NAO variability on the two timescales is associated with different dynamical behaviour in terms of eddy-mean flow interaction, Rossby wave breaking and blocking. The two timescales also exhibit different regional impacts on temperature and precipitation and different relationships to sea surface temperatures. These results are derived from linear regression analysis of the Twentieth Century and NCEP-NCAR reanalyses and of a high-resolution HiGEM General Circulation Model control simulation, with additional analysis of a long sea level pressure reconstruction. Evidence is presented for an influence of the ocean circulation on the longer timescale variability of the NAO, which is particularly clear in the model data. As well as providing new evidence of potential predictability, these findings are shown to have implications for the reconstruction and interpretation of long climate records.

Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation

Background A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. Methods In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. Results Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r2 = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r2 = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r2 = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r2 = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. Conclusions We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.

Masked hypertension and cardiac remodeling in middle-aged endurance athletes

OBJECTIVES: Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). METHODS: Male participants of a 10-mile race were recruited and included if office blood pressure was normal (<140/90 mmHg). Athletes were stratified into a masked hypertension and normotension group by ambulatory blood pressure. Primary endpoint was diastolic function, expressed as peak early diastolic mitral annulus velocity (E'). Left ventricular global strain, left ventricular mass/volume ratio, left atrial volume index, signal-averaged P-wave duration (SAPWD), and SVT during 24-h Holter monitoring were recorded. RESULTS: From 108 runners recruited, 87 were included in the final analysis. Thirty-three (38%) had masked hypertension. The mean age was 42 +/- 8 years. Groups did not differ with respect to age, body composition, cumulative training hours, and 10-mile race time. Athletes with masked hypertension had a lower E' and a higher left ventricular mass/volume ratio. Left ventricular global strain, left atrial volume index, SAPWD, and SVT showed no significant differences between the groups. In multiple linear regression analysis, masked hypertension was independently associated with E' (beta = -0.270, P = 0.004) and left ventricular mass/volume ratio (beta = 0.206, P = 0.049). Cumulative training hours was the only independent predictor for left atrial volume index (beta = 0.474, P < 0.001) and SAPWD (beta = 0.481, P < 0.001). CONCLUSION: In our study, a relevant proportion of middle-aged athletes had masked hypertension, associated with a lower diastolic function and a higher left ventricular mass/volume ratio, but unrelated to left ventricular systolic function, atrial remodeling, or SVT.