Decreased liver-to-spleen ratio in low-dose computed tomography as a biomarker of fatty liver disease reflects risk for myocardial ischaemia.

Aims: A strong association between fatty liver disease (FLD) and coronary artery disease is consistently reported. Our aim was to evaluate whether FLD diagnosed using low-dose non-contrast computed tomography (LDCT), as a by-product of myocardial perfusion imaging (MPI), is associated with myocardial ischaemia or left ventricular function parameters. Methods and results: We analysed 742 patients who had undergone MPI using single photon emission computed tomography (SPECT) and LDCT. A liver-to-spleen ratio (in Hounsfield units) of <1 was defined as FLD. Myocardial ischaemia was defined as a summed difference score (SDS) ≥3. Left ventricular size and systolic function were assessed from the electrocardiogram-gated SPECT. FLD patients were younger (63 vs. 68 years) and had a higher body mass index (34.6 vs. 29.0 kg/m2) and a higher SDS (2.65 vs. 1.63), P < 0.001 for all. Independently of several possible confounding factors including traditional risk factors, patients with FLD had a 1.70-fold risk of ischaemia (95% confidence interval 1.11-2.58, P = 0.014). Left ventricular end-diastolic volume (109 vs. 109 mL) and ejection fraction (61 vs. 61%) were comparable in those with and without FLD (non-significant for both). Conclusions: With the help of LDCT, it is possible to identify FLD, which is associated with an increased risk of myocardial ischaemia. Therefore, evaluation of FLD from LDCT is recommended along with MPI.

Fatty liver disease is the most common liver disease, affecting a quarter of the population worldwide. It is connected to diabetes and high blood pressure as well as to overweight and obesity. Computed tomography is a common diagnostic method. Its downside is that it exposes patients to radiation. Images can be taken with lower doses of radiation, but these images are less clear and often cannot be used for diagnosis. Low-dose computed tomography is often used with other methods of medical imaging, especially for the heart and lungs. This study shows that fatty liver disease can be diagnosed as a free by-product of low-dose computed tomography images gathered as part of other diagnostic imaging. We also show that fatty liver disease diagnosed from these images is connected to reduced blood flow of heart muscle. Based on the findings, we recommend that these images be scanned for fatty liver disease to identify patients who are at higher risk of heart disease.

Decreased Gray-White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea.

BACKGROUND: Very recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-ß deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM-WM contrast. There are no reports on possible changes in this contrast in severe OSA. OBJECTIVES: Evaluate changes in the global [11C]-PiB GM-WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them. DESIGN AND SETTING: Cross-sectional imaging study. PARTICIPANTS: 19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea-Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health. MEASUREMENTS: Detailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM-WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI. RESULTS: Static [11C]-PiB PET uptake showed significantly decreased GM-WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM-WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM-WM contrast was associated with smoking (p = 0.007) and higher Apnea-Hypopnea Index (p = 0.001). CONCLUSIONS: Severe OSA was associated with decreased GM-WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Impact of deep learning-determined smoking status on mortality of cancer patients: never too late to quit.

BACKGROUND: Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm. MATERIALS AND METHODS: This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms. RESULTS: The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models. CONCLUSIONS: Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.

Childhood Oral Infections Associate with Adulthood Metabolic Syndrome: A Longitudinal Cohort Study.

Chronic oral infection/inflammation is cross-sectionally associated with metabolic syndrome (MetS) in adults, but there are few longitudinal studies and studies on childhood oral infections and adult MetS risk. We investigated whether childhood clinical parameters indicative of oral infection/inflammation were associated with adulthood MetS and its components. A total of 755 children aged 6, 9, and 12 y underwent a clinical oral examination in 1980 as part of the Cardiovascular Risk in Young Finns Study. Oral health measures included bleeding on probing (BOP), periodontal probing pocket depth, caries, fillings, and visible plaque. Metabolic parameters were determined at baseline and during follow-up. MetS was diagnosed (n = 588, 77.9%) in the adulthood at 21 y (in 2001), 27 y (in 2007), and 31 y (in 2011) after the oral assessment, when the participants were 27 to 43 y old. Regression analyses were adjusted for childhood age, sex, body mass index, and family income, as well as adulthood smoking and education level. In adulthood, MetS was diagnosed in 11.9% (2001), 18.7% (2007), and 20.7% (2011) of participants at the 3 follow-ups. Childhood caries and fillings were associated with increased risk of adult MetS (risk ratio [95% CI], 1.25 [0.90 to 2.45] and 1.27 [1.02 to 1.99]) and with increased systolic blood pressure (1.78 [1.01 to 4.26] and 2.48 [1.11 to 4.12]) and waist circumference (2.25 [1.02 to 4.99] and 1.56 [1.01 to 3.25]), whereas BOP and visible plaque were associated with plasma glucose (1.97 [1.08 to 3.60] and 1.88 [1.00 to 3.53]). Severity of BOP (P = 0.015) and caries (P = 0.005) and teeth with plaque (P = 0.027) were associated with number of MetS components. No such trends were seen with probing pocket depth. Childhood oral infection/inflammation was associated with adverse metabolic parameters and MetS in adulthood.

The burden of adult asthma in Finland: impact of disease severity and eosinophil count on health care resource utilization.

Objective: To describe health care resource utilization (HCRU) and associated costs in adult patients referred for specialist asthma care in Southwest Finland, by disease severity and blood eosinophil count (BEC).Methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from patients >18 years of age on the hospital register of the Hospital District of Southwest Finland. Data extraction was from January 1, 2004 to December 31, 2015; the index date was the first hospital visit within this period with an International Classification of Diseases-10 diagnosis code for asthma or acute severe asthma. Patients were categorized by asthma severity (based on medication use) and BEC (<300 or ≥300 cells/µL). Total and asthma-related HCRU and estimated costs were recorded the year following index and for calendar years 2004-2015.Results: Overall, 14,398 patients were included; 388 had severe asthma at index. BEC was available for 3781 patients; 1434 had a BEC ≥300 cells/µL and 2347 had a BEC <300 cells/µL. A total of 1241 patients had severe asthma; 270 patients had severe eosinophilic asthma (severe asthma and a BEC ≥300 cells/µL). Patients with severe versus non-severe asthma had higher total- and asthma-related outpatient visits, inpatient days, emergency room visits and costs per patient year; those with BEC ≥300 cells/µL versus <300 cells/µL had more outpatient visits. All recorded HCRU and associated costs were highest in patients with severe eosinophilic asthma.Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic asthma for adults in Finland.

Geographic origin as a determinant of left ventricular mass and diastolic function - the Cardiovascular Risk in Young Finns Study.

AIMS: Eastern Finns have higher risk of coronary heart disease (CHD) and carotid intima-media thickness than western Finns although current differences in CHD risk factors are minimal. Left ventricular (LV) mass and diastolic function predict future cardiovascular events but their east-west differences are unknown. We examined the association of eastern/western baseline origin with LV mass and diastolic function. METHODS: The study population included 2045 subjects of the Cardiovascular Risk in Young Finns Study with data from the baseline survey (1980) and the latest follow-up (2011) when echocardiography was performed at the age of 34-49 years. RESULTS: Subjects with eastern baseline origin had in 2011 higher LV mass (139±1.0 vs. 135±1.0 g, p=0.006) and E/e'-ratio indicating weaker LV diastolic function (4.86±0.03 vs. 4.74±0.03, p=0.02) than western subjects. Results were independent of age, sex, area of examination and CHD risk factors such as blood pressure and BMI (LV mass indexed with height: p<0.0001; E/e'-ratio: p=0.01). LV end-diastolic volume was higher among subjects with eastern baseline origin (135±0.9 vs. 131±0.9 ml, p=0.0011) but left atrial end-systolic volume, also indicating LV diastolic function, was not different between eastern and western subjects (43.4±0.5 vs. 44.0±0.5 ml, p=0.45). Most of the subjects were well within the normal limits of these echocardiographic measurements. CONCLUSIONS: In our healthy middle-aged population, geographic origin in eastern Finland associated with higher LV mass compared to western Finland. Higher E/e'-ratio suggests that subjects with eastern baseline origin might have higher prevalence of diastolic dysfunction in the future than western subjects.

Education as a moderator of genetic risk for higher body mass index: prospective cohort study from childhood to adulthood.

OBJECTIVES: The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. SUBJECTS/METHODS: The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=-0.12 (95% CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education. CONCLUSIONS: In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

Associations of cardiorespiratory fitness, physical activity, and adiposity with arterial stiffness in children.

Associations of cardiorespiratory fitness (CRF), physical activity (PA), sedentary behavior, and body fat percentage (BF%) with arterial stiffness and dilation capacity were investigated in 160 prepubertal children (83 girls) 6-8 years of age. We assessed CRF (watts/lean mass) by maximal cycle ergometer exercise test, total PA, structured exercise, unstructured PA, commuting to and from school, recess PA and total and screen-based sedentary behavior by questionnaire, BF% using dual-energy X-ray absorptiometry, and arterial stiffness and dilation capacity using pulse contour analysis. Data were adjusted for sex and age. Poorer CRF (standardized regression coefficient ß = -0.297, P < 0.001), lower unstructured PA (ß = -0.162, P = 0.042), and higher BF% (ß = 0.176, P = 0.044) were related to higher arterial stiffness. When CRF, unstructured PA, and BF% were in the same model, only CRF was associated with arterial stiffness (ß = -0.246, P = 0.006). Poorer CRF was also related to lower arterial dilation capacity (ß = 0.316, P < 0.001). Children with low CRF (< median) and high BF% (≥ median; P = 0.002), low CRF and low unstructured PA (< median; P = 0.006) or children with low unstructured PA and high BF% (P = 0.005) had higher arterial stiffness than children in the opposite halves of these variables. Poor CRF was independently associated with increased arterial stiffness and impaired arterial dilation capacity among children.

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

BACKGROUND/OBJECTIVES: Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. SUBJECTS/METHODS: Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. RESULTS: Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. CONCLUSIONS: Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

Interaction of NPSR1 genotypes and probiotics in the manifestation of atopic eczema in early childhood

BACKGROUND: Neuropeptide S Receptor (NPSR1) gene has been associated with multiple allergic phenotypes in several patient populations. OBJECTIVE: We analysed the effect of the NPSR1 genotypes in the development of asthma, rhinitis, eczema, or food allergy in children randomly receiving either probiotic or placebo treatment. METHODS: 796 children born to families at high risk for allergic diseases were examined by a paediatrician at the age of three months, six months, two years, and five years. Asthma, rhinitis, eczema, and food allergy were diagnosed according to international guidelines. Treatment with probiotics (double-blinded and placebo controlled) was begun with mothers at 35 weeks of gestation age and continued after the birth of infants up to the age of six months. Association and additive inheritance models were used in genetic analyses. RESULTS: Distribution of the hopo546333 was suggestive in the group of patients with atopic eczema at two years. The hopo546333_G was found more often in those with eczema in the placebo group (p = 0.048, after Bonferroni correction) and the hopo546333_A was found more often in those with eczema and probiotics compared to those with eczema and placebo treatment. None of the NPSR1 tagging SNPs was associated with asthma, IgE-mediated asthma, or sensitisation. Allergic disease in both parents doubled the risk for IgE-mediated allergic disease (OR 2.1). CONCLUSIONS: The NPSR1 gene SNP hopo546333 showed a suggestive association for high IgE-associated atopic eczema at two years

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Longitudinal HRQoL shows divergent trends and identifies constant decliners in asthma and COPD.

BACKGROUND/AIM: Monitoring of lung function alone does not adequately identify the high-risk patients among elderly asthma and COPD cohorts. The additional value of Health-Related Quality of Life (HRQoL) development in the detection of patients with a disabling disease in clinical practice is unclear. The aim of this study was to statistically examine the individual development of HRQoL measured using respiratory-specific AQ20 and generic 15D questionnaires. MATERIALS AND METHODS: The HRQoL of COPD (N = 739) and asthma (N = 1329) patients was evaluated at 0, 1, 2, and 4 years after recruitment. To determine a five-year HRQoL change for each patient we used mixed-effects modelling for linear trend. RESULTS: In COPD, the majority (60-80%) of the individuals showed declining trend, whereas in asthma, the majority (46-71%) showed no attenuation in HRQoL. The proportion of constant decliners was estimated higher with the 15D both in asthma (6.3%) and COPD (6.3%) than with AQ20 (3.5 and 4.5%, respectively). The first measurement of HRQoL was found to predict future development of HRQoL. In asthma, obesity-related diseases such as hypertension, diabetes and gastro-esophageal reflux disease best explained the decline, whereas in COPD, age and the level of bronchial obstruction were the main determinants. CONCLUSION: Based on the five-year follow-up, the HRQoL trends significantly diverging from each other could be identified both among the asthma and COPD patients. Compared to cross-sectional HRQoL, the HRQoL trend over a clinically relevant period of time allows us to ignore, to a great extent, the random error of self-assessed HRQoL and thus, it may offer a more accurate measure to describe the disease process.

Axial and radial waveforms in common carotid artery: an advanced method for studying arterial elastic properties in ultrasound imaging.

Our objective was to develop a method for studying the biomechanics of the common carotid artery (CCA) by evaluating both radial and less known axial distension of the arterial wall. We developed software capable of tracking the movements of different arterial wall layers from ultrasound recordings of CCA, and we then calculated several indices of arterial stiffness. The wide spectrum of arterial stiffness indices defined from one measurement is a unique feature of our method. The motion-tracking algorithm is based on 2-D cross-correlation enhanced with luminance optimizations. The repeatability and reproducibility of the motion tracking were evaluated by performing 10-s ultrasound recordings of left CCA twice to 19 healthy volunteers (11 women, 8 men, age 41.3 ± 14.3 y). The method revealed a biphasic axial movement of the CCA and demonstrated that the indices of arterial stiffness defined from radial movement of carotid artery are reproducible (Cronbach's α, 0.59-0.97) as well as the indices from axial movement are reproducible (Cronbach's α, -0.68 to 0.93). The good reproducibility of the motion tracking is evidence that this method of studying arterial elastic properties is adequate for in vivo studies.

Successful Smoking Cessation in COPD: Association with Comorbidities and Mortality.

Smoking cessation is the cornerstone of COPD management, but difficult to achieve in clinical practice. The effect of comorbidities on smoking cessation and risk factors for mortality were studied in a cohort of 739 COPD patients recruited in two Finnish University Hospitals. The diagnosis of COPD was done for the first time on average 5.5 years prior to the enrollment. Data from the medical records and followup questionnaires (years 0, 1, 2, and 4) have been analyzed. The patients' lung function varied greatly; mean FEV(1) 58% of predicted. A total of 60.2% of men and 55.6% of women had been able to quit smoking. Alcohol abuse (OR 2.1, 95% CI 1.4-3.3) and psychiatric conditions (OR 1.8, 95% CI 1.2-2.7) were strongly related to low success rates of quitting. Among current smokers high nicotine dependency was again explained by alcohol abuse and psychiatric conditions. Non-quitters were younger than quitters, but their mortality rates remained significantly higher even when the model was adjusted for impairment of lung functions and comorbidities. In conclusion, co-existing addiction and psychiatric diseases significantly decreased the success rates in smoking cessation and increased mortality among the patients.

Dietary factors associated with overweight and body adiposity in Finnish children aged 6-8 years: the PANIC Study.

OBJECTIVES: To investigate the associations of dietary factors with overweight, body fat percentage (BF%), waist circumference (WC) and hip circumference (HC) among children. DESIGN: Cross-sectional analysis of the Physical Activity and Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged 6-8 years from Kuopio, Finland. METHODS: The children's weight, height, WC and HC were measured. Overweight was defined by International Obesity Task Force body mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry, nutrient intakes and meal frequency by 4-day food records and eating behaviour by Children's Eating Behaviour Questionnaire. RESULTS: Daily consumption of all the three main meals was inversely associated with overweight (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.18-0.75), BF% (ß -0.12, P = 0.012), WC (ß -0.16, P = 0.002) and HC (ß -0.15, P = 0.002). Enjoyment of food, food responsiveness and emotional overeating were directly associated with overweight (OR 1.57, 95% CI 1.04-2.35; OR 4.68, 95% CI 2.90-7.54; OR 2.60, 95% CI 1.52-4.45, respectively), BF% (ß 0.13, P = 0.004; ß 0.30, P<0.001; ß 0.09, P = 0.035, respectively), WC (ß 0.14, P = 0.003; ß 0.40, P<0.001; ß 0.19, P<0.001, respectively) and HC (ß 0.15, P = 0.001; ß 0.38, P<0.001; ß 0.15, P = 0.001, respectively). Satiety responsiveness was inversely associated with overweight (OR 0.42, 95% CI 0.26-0.67), BF% (ß -0.20, P<0.001), WC (ß -0.26, P<0.001) and HC (ß -0.26, P<0.001). Slowness in eating was inversely associated with overweight (OR 0.61, 95% CI 0.41-0.92), WC (ß -0.16, P = 0.001) and HC (ß -0.17, P<0.001). Protein intake was directly associated with BF% (ß 0.11, P = 0.017), WC (ß 0.11, P = 0.020) and HC (ß 0.13, P = 0.008). CONCLUSIONS: Promoting regular consumption of main meals and healthy eating behaviours should be emphasized in the prevention of overweight among children. More research is needed on the association of protein-rich foods with body adiposity in children.

Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study.

Human cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima-media thickness, carotid artery distensibility and brachial artery flow-mediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24-39 years) taking part in the Cardiovascular Risk in Young Finns study. CMV antibody titres were significantly higher in women compared to men. In men, high CMV antibody titres were associated directly with age (P < 0·001) and systolic (P = 0·053) and diastolic (P = 0·002) blood pressure elevation, and associated inversely with flow-mediated dilation (P = 0·014). In women, CMV antibody titres did not associate with any of the analysed parameters. In a multivariate regression model, which included traditional atherosclerotic risk factors, CMV antibody titres were independent determinants for systolic (P = 0·029) and diastolic (P = 0·004) blood pressure elevation and flow-mediated dilation (P = 0·014) in men. High CMV antibody titres are associated independently with blood pressure and brachial artery flow-mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age.

Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd : implications to delayed myelination and oligodendrocyte maturation.

AIMS: CLN8 deficiency underlies one of a group of devastating childhood neurodegenerative disorders, the neuronal ceroid lipofuscinoses. The function of the CLN8 protein is currently unknown, but a role in lipid metabolism has been proposed. In human CLN8 diseased brains, alterations in lipid composition have been detected. To further investigate the connection of CLN8 to lipid metabolism, we characterized the lipid composition of early symptomatic Cln8-deficient mouse (Cln8(mnd)) brains. METHODS: For lipid profiling, Cln8(mnd) cerebral cortical tissue was analysed by liquid chromatography/mass spectrometry. Galactolipid synthesis was measured through enzyme activity and real-time mRNA expression analyses. Based on the findings, myelination and white matter integrity were studied by immunohistochemistry, stereological methods, electron microscopy and magnetic resonance imaging. The development of myelin-forming oligodendrocytes was also studied in vitro. RESULTS: Sphingolipid profiling showed a selective reduction in myelin-enriched galactolipids. The mRNA expression and activity of UDP-galactose:ceramide galactosyltransferase (CGT), the key enzyme in the galactolipid synthesis, was reduced in the Cln8(mnd) brain. Expression of oligodendrocyte markers suggests a maturation defect. The amount of myelin was reduced in 1-month-old Cln8(mnd) mice, but reached normal levels by 5 months of age. The level of Cln8 gene expression followed the developmental pattern of myelin formation and was high in primary oligodendrocytes. CONCLUSIONS: Taken together, these observations suggest that galactolipid deficiency and delayed myelin maturation characterize the early CLN8 disease pathogenesis through a maturation defect of oligodendrocytes.

Clinical audit: Development of the criteria of good practices.

Clinical audit is a systematic review of the procedures in order to improve the quality and the outcome of patient care, whereby the procedures are examined against agreed standards for good medical RADIOLOGICAL procedures. The criteria of good procedures (i.e. the good practice) are thus the cornerstones for development of clinical audits: these should be the basis of assessments regardless of the type of the audit--external, internal, comprehensive or partial. A lot of criteria for good practices are available through the recommendations and publications by international and national professional societies and other relevant organisations. For practical use in clinical audits, the criteria need to be compiled, sorted out and agreed on for the particular aims of an audit (comprehensive or partial, external or internal). The national professional and scientific societies can provide valuable contribution to this development. For examination--or treatment-specific criteria--preliminary consensus needs to be obtained with the help of clinical experts, while clinical audits can be useful as a benchmarking tool to improve the criteria.

Dynamic estimation of cardiac repolarization characteristics during hypoglycemia in healthy and diabetic subjects.

Hypoglycemia is known to affect the repolarization characteristics of the heart, but the mechanisms behind these changes are not completely understood. We analyzed repolarization characteristics continuously from 22 subjects during normoglycemic period, transition period (blood glucose concentration decreasing) and hypoglycemic period from nine healthy controls (Healthy), six otherwise healthy type 1 diabetics (T1DM) and seven type 1 diabetics with disease complications (T1DMc). An advanced principal component regression (PCR)-based method was used for estimating ECG parameters beat-by-beat, and thus, continuous comparison between the repolarization characteristics and blood glucose values was made. We observed that hypoglycemia related ECG changes in the T1DMc group were smaller than changes in the Healthy and T1DM groups. We also noticed that when glucose concentration remained at a low level, the heart rate corrected QT interval prolonged progressively. Finally, a few minutes time lag was observed between the start of hypoglycemia and cardiac repolarization changes. One explanation for these observations could be that hypoglycemia related hormonal changes have a significant role behind the repolarization changes. This could explain at least the observed time lag (hormonal changes are slow) and the lower repolarization changes in the T1DMc group (hormonal secretion lowered in long duration diabetics).

Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance.

AIMS: The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. METHODS: Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up, were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention, we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA(1c,) serum lipids and blood pressure were carried out. RESULTS: Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P<0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA(1c) . Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. CONCLUSIONS: Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.