Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder.

Recent data have emphasized the role of inflammation and intestinal immunoglobulin A (IgA) responses in the pathogenesis of alcoholic liver disease (ALD). In order to further explore such associations, we compared IgA titers against antigens targeted to ethanol metabolites and tissue transglutaminase with pro- and anti-inflammatory mediators of inflammation, markers of liver status, transferrin protein desialylation and extracellular matrix metabolism in alcohol-dependent patients with or without liver disease and in healthy controls. Serum IgAs against protein adducts with acetaldehyde (HbAch-IgA), the first metabolite of ethanol, and tissue transglutaminase (tTG-IgA), desialylated transferrin (CDT), pro- and anti-inflammatory cytokines, markers of liver status (GT, ALP) and extracellular matrix metabolism (PIIINP, PINP, hyaluronic acid, ICTP and CTx) were measured in alcohol-dependent patients with (n = 83) or without (n = 105) liver disease and 88 healthy controls representing either moderate drinkers or abstainers. In ALD patients, both tTG-IgA and HbAch-IgA titers were significantly higher than those in the alcoholics without liver disease (p < 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (p = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, p < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p < 0.0005), CDT (rs = 0.413, p < 0.0001), GT (rs = 0.487, p < 0.0001), alkaline phosphatase (rs = 0.466, p < 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p < 0.0001), hyaluronic acid (rs = 0.575, p < 0.0001), ICTP (rs = 0.482, p < 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p < 0.0001), IL-8 (rs = 0.535, p < 0.0001) and TNF-α (rs = 0.591, p < 0.0001), whereas significant inverse correlations were observed with serum TGF-ß (rs = -0.366, p < 0.0001) and CTx, a marker of collagen degradation (rs = -0.495, p < 0.0001). The data indicate that the induction of IgA immune responses toward ethanol metabolites and tissue transglutaminaseis a characteristic feature of patients with AUD and coincides with the activation of inflammation, extracellular matrix remodeling and the generation of aberrantly glycosylated proteins. These processes appear to work in concert in the sequence of events leading from heavy drinking to ALD.

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites.

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

Fear of childbirth after medical vs surgical abortion. Population-based register study from Finland.

INTRODUCTION: To evaluate the effect of method of induced abortion and other abortion-associated variables on the incidence of fear of childbirth in subsequent pregnancy. MATERIAL AND METHODS: This population-based register study cohort includes all nulliparous women with their first pregnancy ending in an induced abortion in 2000-2015 and subsequent pregnancy with live singleton delivery between 2000 and 2017 (n = 21 479). Data were derived from three national registers maintained by the Finnish Institute for Health and Welfare. We divided the study population in three cohorts: (a) medical and (b) surgical abortion during first trimester (≤84 days of gestation), and (c) medical abortion during second trimester (85-168 days of gestation). Primary outcome measures were the incidence of registry-identified fear of childbirth and cesarean delivery related to it. RESULTS: The overall incidence of fear of childbirth was 5.6% (n = 1209). Altogether, 19.2% (n = 4121) of women underwent cesarean delivery. The odds were elevated especially for elective cesarean delivery (odds ratio [OR] 9.30, 95% CI 7.95-10.88, P < .001) in women with fear of childbirth. In multivariable analysis, the odds for fear of childbirth (adjusted OR [aOR] 0.80, 95% CI 0.68-0.94) and cesarean delivery (aOR 0.66, 95% CI 0.84-0.90) were decreased in women with a history of first-trimester medical abortion compared with those with first-trimester surgical abortion. Second-trimester medical abortion had no effect on the odds for fear of childbirth (aOR 1.04, 95% CI 0.71-1.50). Maternal age of 30-39 years and interpregnancy interval over 2 years were additional risk factors for both fear of childbirth and cesarean delivery, but surgical evacuation of uterus after the abortion was not. CONCLUSIONS: One first- or second-trimester medical abortion does not increase the odds for fear of childbirth, and cesarean delivery related to it in subsequent pregnancy when compared with first-trimester surgical abortion. Older maternal age and longer interpregnancy interval emerged as risk factors for fear of childbirth.

Combined effects of lifestyle risk factors on fatty liver index.

BACKGROUND: Factors of lifestyle may have a major impact on liver-related morbidity and mortality. We examined independent and joint effects of lifestyle risk factors on fatty liver index (FLI), a biomarker of hepatic steatosis, in a population-based cross-sectional national health survey. METHODS: The study included 12,368 participants (5784 men, 6584 women) aged 25-74 years. Quantitative estimates of alcohol use, smoking, adiposity and physical activity were used to establish a total score of risk factors, with higher scores indicating an unhealthier lifestyle. FLI was calculated based on an algorithm including body mass index, waist circumference, serum gamma-glutamyltransferase and triglycerides. RESULTS: The occurrence of FLI ≥ 60% indicating fatty liver increased from 2.4% in men with zero risk factors to 81.9% in those with a total risk score of 7-8 (p <  0.0005 for linear trend) and in women from 0 to 73.5% (p <  0.0005). The most striking individual impacts on the likelihood for FLI above 60% were observed for physical inactivity (p <  0.0005 for both genders) and alcohol consumption (p <  0.0005 for men). Interestingly, coffee consumption was also found to increase with increasing risk factor scores (p <  0.0005 for linear trend in both genders). CONCLUSIONS: The data indicates that unfavorable combinations of lifestyle risk factors lead to a high likelihood of hepatic steatosis. Use of FLI as a diagnostic tool may benefit the assessment of interventions aimed at maintaining a healthy lifestyle and prevention of liver-related morbidity.

Assessment of alcohol consumption in depression follow-up using self-reports and blood measures including inflammatory biomarkers.

AIMS: Alcohol consumption has been suggested a major role in the pathogenesis and prognosis of depression. However, reliable identification of hazardous drinking continues to be problematic. We compared the accuracy of different biomarkers and self-reports of alcohol consumption in the follow-up study of depression. METHODS: Data from 202 patients with major depressive disorder were obtained through self-reports, AUDIT and AUDIT-C questionnaires and biomarker analyses. The clinical assessments and measurements of biomarkers (GT, CDT, GT-CDT-combination, MCV, ALT, AST, hs-CRP, IL-6) were performed at baseline and after six months of treatment. Based on self-reported alcohol intake at baseline the patients were classified to three subgroups. RESULTS: About 27.2% of patients were categorized to high-risk drinkers, 26.3% low-risk drinkers and 46.5% abstainers. High-risk drinkers showed significantly higher mean values of GT, CDT, GT-CDT-combination and IL-6 than abstainers, diagnostic accuracy being highest with the combined marker of GT-CDT. The accuracy of AUDIT and AUDIT-C to detect high-risk drinking was also significant. During follow-up, the differences observed in the biomarkers at baseline disappeared together with recovery from depression. CONCLUSIONS: Our data suggest the combined use of GT-CDT and AUDIT questionnaires to improve the identification of drinking of patients with depression. This approach could be useful for improving treatment adherence and outcome in depressed patients.

Laboratory test based assessment of WHO alcohol risk drinking levels.

Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25-74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.

Life style habits, biochemical factors and their interaction in the prediction of incident hypertension during 21-year follow-up.

BACKGROUND: Hypertension is a global health threat and major cardiovascular risk. Various risk-prediction models for incident hypertension have been developed but not many of them have studied the risk-predictive value of life style factors in combination with cardiovascular biomarkers during long-term period of over 10 years. METHODS: We examined differences in several classical variables for 299 subjects in OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort in subjects with no or new hypertension during a follow-up period of 21 years. Effect of both various life style habits and biomarkers were investigated. RESULTS: Baseline blood pressure, being overweight and smoking actively were independent predictors of new hypertension in majority of multivariate models during long-term follow-up of 21 years in subjects without previous hypertension. Increased high-sensitive C-reactive protein (hsCRP) level (> 3 mg/L) was the strongest predictor of incident hypertension in univariate model. Subjects with two or all three of main risk factors (being overweight, smoking actively and having high hsCRP) had 4-fold risk for incident hypertension. CONCLUSIONS: Smoking, overweight and increased hsCRP level had risk-predictive value in incident hypertension prediction during long-term follow-up of 21 years. Assessment and measurement of these parameters could be used in help of detecting high risk subjects and primary prevention of hypertension very early on. In addition, the study shows that blood pressure at the middle-age should be followed and treated intensively to prevent hypertension in the older age. KEY MESSAGES: Baseline blood pressure, being overweight and smoking actively are independent predictors of new hypertension during a long-term follow-up of 21 years. Having two or all three risk factors (smoking actively, body mass index over 25 kg/m2, high-sensitive C-reactive protein (hsCRP) level over 3 mg/L) indicates a 4-fold risk for incident hypertension within 21-year follow-up.

Towards national comprehensive gestational diabetes screening - consequences for neonatal outcome and care.

INTRODUCTION: The change from risk-factor-based to nearly comprehensive screening of gestational diabetes (GDM) identifies more but milder cases of the disease. The main aim of this study was to evaluate the effect of this screening policy change on neonatal outcomes and care. MATERIAL AND METHODS: A population-based register study in Finland. GDM cases during risk-factor-based (year 2006, n = 5179) and comprehensive (2010, n = 6679) screenings were identified through the Medical Birth Register. All singletons without maternal GDM or prepregnancy diabetes served as controls (n = 51 746 and n = 52 386, respectively). The main outcomes were macrosomia, neonatal hypoglycemia and the need for care in a neonatal ward. RESULTS: In the GDM group, the mean birthweight decreased between the study years from 3660 g to 3595 g and the prevalence of macrosomia from 5.6 to 4.1% even after adjustment for maternal age, parity and prepregnancy body mass index. The adjusted mean difference in birthweight between GDM and control newborns decreased from 70 to 22 g between the study years. The prevalence of neonatal hypoglycemia increased from 18.0 to 22.1% in the GDM group. However, neonatal hypoglycemia was more often treated without care in a neonatal ward. The proportion of infants treated on a neonatal ward decreased in both the GDM and control groups between the study years. CONCLUSIONS: In newborns, comprehensive GDM screening led to decreased mean birthweight and macrosomia rates, but the prevalence of neonatal hypoglycemia increased. This places substantial demands for delivery hospitals and healthcare resources.

Population-Based Study of Prediagnostic Antibodies to Chlamydia trachomatis in Relation to Adverse Pregnancy Outcome.

BACKGROUND: Chlamydia trachomatis infection is one of the most common sexually transmitted reported bacterial infections worldwide. The well-known sequelae of chlamydial infection include pelvic inflammatory disease and tubal factor infertility, but the evidence linking C. trachomatis infection and adverse pregnancy outcome is inconsistent and has been largely based on case-control studies with limited study populations. We evaluated this link in a population-based longitudinal biobank health registry setting. METHODS: The association between C. trachomatis major outer membrane protein (MOMP) peptide-specific IgG antibodies and ectopic pregnancy, miscarriage, and preterm delivery was examined in a prospective case-control study nested in the Finnish Maternity Cohort. Ectopic pregnancy and miscarriage cases were identified through the Hospital Discharge Register 1998-2005; cases with preterm deliveries were identified through the Finnish Medical Birth register 1988-2005. Control samples were retrieved from the Finnish Maternity Cohort serum bank. A total of 800 cases of ectopic pregnancy, 800 cases of miscarriage, and 1350 cases of preterm birth were included. Equal number of pregnant women without the outcome diagnosis served as controls. The cases and controls were matched by sampling time, at the serum sampling and postal code district. RESULTS: Antichlamydial IgG antibodies were associated with ectopic pregnancy. Positive antibody levels were found in 21.0% of cases and 14.6% of controls (P = 0.001; odds ratio, 1.56; 95% confidence interval, 1.20-2.03). Previous exposure to C. trachomatis, as indicated by serum antibodies, doubled the risk of ectopic pregnancy within age and was highest among women 35 years or older. Antichlamydial IgG antibody rates between the cases with miscarriage (16.3% in cases vs. 16.8% in controls) or preterm delivery (18.1% vs. 18.1%) and controls did not differ. CONCLUSIONS: Our findings confirm the association between previous exposure to C. trachomatis and ectopic pregnancy. We found no association between C. trachomatis seropositivity and miscarriage or preterm birth.

Fetal Alcohol Syndrome and Maternal Alcohol Biomarkers in Sera: A Register-Based Case-Control Study.

BACKGROUND: Fetal alcohol syndrome (FAS) is a well-known consequence of prenatal alcohol exposure. However, women tend to deny or underreport their alcohol use during pregnancy. The aim of this study was to explore the usability of various alcohol biomarkers for FAS screening in a data set without information on self-reported alcohol use. METHODS: A nationwide register study with a case-control design was conducted. The target population consisted of all live births in Finland from 1987 to 2005. FAS cases (n = 565) were identified from the Finnish Register of Congenital Malformations. Mothers of FAS cases and their controls were selected in a ratio of 1 to 2 from the Finnish Maternity Cohort (FMC). Background information was obtained from the Finnish Medical Birth Register. Serum samples, collected at the mother's first visit to the maternity care, were obtained from the national FMC biobank. Biomarkers of alcohol consumption, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (%CDT), combination of GGT and CDT (GGT-CDT), and ethylglucuronide (EtG) were analyzed from mothers of FAS cases (n = 385) and their controls (n = 745). RESULTS: Median levels of all biomarkers were significantly higher among the mothers of FAS children than in control mothers. Using previously validated cutoffs for EtG, GGT, %CDT, and GGT-CDT, nearly half (46%) of the mothers with affected offspring could be identified. The predictive association was highest for GGT-CDT combination and significant also for all the other biomarkers. CONCLUSIONS: In this explorative case-control study, we demonstrate that the FMC biobank can be used to screen alcohol biomarkers for epidemiological research purposes. According to our results, the use of alcohol biomarkers during the first trimester may help to identify the high-risk pregnancies for FAS. A more systematic use of alcohol biomarkers at maternity care may open new possibilities for screening and intervention of alcohol use among pregnant mothers.

Assays of Gamma-Glutamyl Transferase and Carbohydrate-Deficient Transferrin Combination from Maternal Serum Improve the Detection of Prenatal Alcohol Exposure.

BACKGROUND: Alcohol use during pregnancy leads to detrimental effects on fetal development. As self-reports by mothers are known to be unreliable for assessing prenatal alcohol exposure, there is a need for sensitive and specific biomarkers for identifying those at risk for alcohol-affected offspring. METHODS: We measured serum gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), a mathematically formulated combination of GGT and CDT (GGT-CDT), and ethylglucuronide (EtG) concentrations from 1,936 mothers with a positive (n = 480) or negative (n = 1,456) history of alcohol use at the time of pregnancy. The material included 385 alcohol-abusing mothers who subsequently gave birth to children with fetal alcohol syndrome (FAS) and 1,551 mothers without FAS children including 95 women who reported a median of 1.0 standard drinks of alcohol per day during pregnancy and 1,456 nondrinking controls. Among those without FAS outcome, there were 405 mothers with gestational diabetes mellitus (GDM) and 745 mothers representing lifelong abstainers. RESULTS: Mothers of FAS children had higher mean GGT, CDT, GGT-CDT, and EtG levels than abstainers (p < 0.001 for all comparisons) or mothers reporting some alcohol consumption but whose children were not diagnosed with FAS (p < 0.001 for all comparisons). In receiver operating characteristic analyses using cutoffs based on abstainers, the area under the curves (AUCs) for GGT-CDT (0.873) were higher than those of GGT (0.824), CDT (0.776), or EtG (0.584) for differentiating the mothers of FAS children and abstainers. Unlike CDT, this combination marker also differed significantly between drinking mothers without FAS outcome and abstainers (AUC = 0.730, p < 0.001). In comparisons adjusted for GDM and body mass index, the group of mothers who had reported a median of 1.0 standard drinks of alcohol per day during pregnancy also differed from the group reporting no current alcohol intake in GGT (p < 0.02) and GGT-CDT (p < 0.01) levels. CONCLUSIONS: Combination of GGT and CDT improves the identification of prenatal alcohol exposure and associated high-risk pregnancies. A more systematic use of biomarkers may help intervention efforts to prevent alcohol-induced adverse effects on fetal development.

Aging fatherhood in Finland - first-time fathers in Finland from 1987 to 2009.

AIM: The increase in maternal age has been well documented in Western societies, but information on paternal age trends is scarce. The aim of this study was to investigate changes in age and other background characteristics of first-time fathers in Finland in the period 1987-2009. MATERIALS AND METHODS: A random 60% sample of first-time fathers in each year from 1987 to 2009 was obtained from Statistics Finland (n=344,529). Five-year intervals were used (three years in 1987-1989). Sociodemographic characteristics of older first-time fathers (⩾40 years) were compared over time using logistic regression. In the logistic regression, immigrants were excluded from the study population as they may have had children before migrating to Finland. RESULTS: The mean age of first-time fathers increased from 28.7 to 30.4 years in 1987-2009. The change was greatest in the Capital Region and smallest in Northern and Eastern Finland. Fatherhood at the age of ⩾40 years doubled from 3.1% to 6.8%. From 2005 to 2009, men who lived in rural areas and the Capital Region, had a long education, were divorced or widowed, had been born in a rural area and were native Finnish speakers, were more likely than other men to be old when they became fathers. CONCLUSIONS DURING THE STUDY PERIOD, THE AVERAGE AGE OF FIRST-TIME FATHERS INCREASED BY TWO YEARS FURTHER STUDIES ARE NEEDED TO EXAMINE WHETHER DELAYS IN FIRST-TIME FATHERHOOD AFFECT FERTILITY, CHILD HEALTH AND THE USE OF SOCIAL AND HEALTH SERVICES.

Influenza C virus infection in military recruits--symptoms and clinical manifestation.

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.

Offspring's blood pressure and metabolic phenotype after exposure to gestational hypertension in utero.

The aim of the study was to investigate the impact of de novo hypertension in pregnancy, i.e. gestational (non-proteinuric) hypertension (GH) and preeclampsia (PE), on the long-term metabolic outcome of the offspring. Data was obtained from the Northern Finland Birth Cohort 1986 (NFBC 1986), including 9,362 pregnancies and subsequent births between 1985 and 1986. Pregnancies were categorised into three groups: (1) GH with blood pressure (BP) ≥ 140/90 mmHg, (2) PE with BP ≥ 140/90 mmHg and proteinuria, and (3) reference group with normal BP. The final study population included 331 offspring of mothers with GH, 197 with PE and 5,045 offspring of normotensive mothers. The main outcome measures were systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), body mass index (BMI), and serum lipid, glucose and insulin levels of the 16 year-old offspring. The children of mothers with GH had higher BP compared to the reference group (SBP percentage difference 2.7 (95% CI 1.6, 3.8); DBP 3.4 (2.1, 4.6); MAP 3.1 (2.0, 4.1), P < 0.001 for all) and a tendency towards higher cholesterol and apolipoprotein B values. The offspring of mothers with PE had higher DBP and MAP, however after the adjustments this difference disappeared. Maternal de novo hypertension during pregnancy is associated with offspring's elevated blood pressure level already in adolescence. GH may also be associated with unfavourable lipid profile of the offspring.

Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample.

While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p <0.0005 for both genders), smoking (GGT: p <0.0005 for men, p =0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p <0.0005; ALT: p <0.0005 for men, p <0.05 for women) and coffee consumption (p <0.0005 for GGT in both genders; p <0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p <0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions.

Genotypic and phenotypic characterization of carriage and invasive disease isolates of Neisseria meningitidis in Finland.

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.

An increasing proportion of reported Chlamydia trachomatis infections are repeated diagnoses.

BACKGROUND: In recent decades, increasing rates of Chlamydia cases have contrasted with decreasing Chlamydia trachomatis seroprevalence rates and decreasing Chlamydia-associated complication rates. We elucidated the conflicting trends by studying incidence of repeated Chlamydia infections over time. METHODS: Chlamydia cases reported during 1995 to 2009 were identified in the Finnish National Infectious Diseases Registry. Trends of single and repeated diagnoses of Chlamydia infection were analyzed. RESULTS: Our study population comprised 147,148 individuals with a total of 177,138 genital chlamydial infections. The proportion of annual repeated diagnoses of genital infections increased among female and males from 4.9% to 7.3% and from 3.8% to 5.3%, respectively. In 2009, 24.8% of the females and 20.3% of the males had had an earlier Chlamydia infection ever during the follow-up time. Of all the repeated diagnoses, 34.1% occurred within 12 months. The highest rates of repeated infection diagnoses occurred in 25-year-old women (37.0%) and in 29-year-old men (30.9%) in a cohort of individuals born in 1979. CONCLUSIONS: A gradual increase of repeated Chlamydia infections resulted in 43% increase in annual infections between 1996 and 2009. The result is supportive of the existing seroprevalence data suggesting that Chlamydia infection burden is not increasing in the whole population. The increasing infection rates in males, in particular, justify development of effective strategy in preventing reinfections and onward transmission.

Impact of Physical Activity on the Characteristics and Metabolic Consequences of Alcohol Consumption: A Cross-Sectional Population-Based Study.

Sedentary lifestyle and excessive alcohol drinking are major modifiable risk factors of health. In order to shed further light on the relationships between physical activity and health consequences of alcohol intake, we measured biomarkers of liver function, inflammation, lipid status and fatty liver index tests in a large population-based sample of individuals with different levels of physical activity, alcohol drinking and other lifestyle risk factors. The study included 21,050 adult participants (9940 men, 11,110 women) (mean age 48.2 ± 13.3 years) of the National FINRISK Study. Data on physical activity, alcohol drinking, smoking and body weight were recorded. The participants were classified to subgroups according to gender, levels of physical activity (sedentary, low, moderate, vigorous, extreme), alcohol drinking levels (abstainers, moderate drinkers, heavy drinkers) and patterns (regular or binge, types of beverages preferred in consumption). Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Physical activity was linearly and inversely related with the amount of alcohol consumption, with the lowest alcohol drinking levels being observed in those with vigorous or extreme activity (p < 0.0005). Physically active individuals were less frequently binge-type drinkers, cigarette smokers or heavy coffee drinkers than those with sedentary activity (p < 0.0005 for linear trend in all comparisons). In the General Linear Model to assess the main and interaction effects of physical activity and alcohol consumption on biomarker status, as adjusted for anthropometric measures, smoking and coffee consumption, increasing levels of physical activity were found to be associated with more favorable findings on serum GGT (p < 0.0005), ALT (p < 0.0005 for men), cholesterol (p = 0.025 for men; p < 0.0005 for women), HDL-cholesterol (p < 0.0005 for men, p = 0.001 for women), LDL-cholesterol (p < 0.03 for men), triglycerides (p < 0.0005 for men, p < 0.03 for women), CRP (p < 0.0005 for men, p = 0.006 for women) and fatty liver index (p < 0.0005). The data support the view that regular moderate to vigorous physical activity may counteract adverse metabolic consequences of alcohol consumption on liver function, inflammation and lipid status. The role of physical activity should be further emphasized in interventions aimed at reducing health problems related to unfavorable risk factors of lifestyle.

Alcohol Drinking Patterns and Laboratory Indices of Health: Does Type of Alcohol Preferred Make a Difference?

Although excessive alcohol consumption is a highly prevalent public health problem the data on the associations between alcohol consumption and health outcomes in individuals preferring different types of alcoholic beverages has remained unclear. We examined the relationships between the amounts and patterns of drinking with the data on laboratory indices of liver function, lipid status and inflammation in a national population-based health survey (FINRISK). Data on health status, alcohol drinking, types of alcoholic beverages preferred, body weight, smoking, coffee consumption and physical activity were recorded from 22,432 subjects (10,626 men, 11,806 women), age range 25-74 years. The participants were divided to subgroups based on the amounts of regular alcohol intake (abstainers, moderate and heavy drinkers), patterns of drinking (binge or regular) and the type of alcoholic beverage preferred (wine, beer, cider or long drink, hard liquor or mixed). Regular drinking was found to be more typical in wine drinkers whereas the subjects preferring beer or hard liquor were more often binge-type drinkers and cigarette smokers. Alcohol use in all forms was associated with increased frequencies of abnormalities in the markers of liver function, lipid status and inflammation even at rather low levels of consumption. The highest rates of abnormalities occurred, however, in the subgroups of binge-type drinkers preferring beer or hard liquor. These results demonstrate that adverse consequences of alcohol occur even at moderate average drinking levels especially in individuals who engage in binge drinking and in those preferring beer or hard liquor. Further emphasis should be placed on such patterns of drinking in policies aimed at preventing alcohol-induced adverse health outcomes.

Elevated One-Hour Post-Load Glucose Is Independently Associated with Albuminuria: A Cross-Sectional Population Study.

The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0 mg/mmol. Compared with those without albuminuria, participants with albuminuria had significantly higher 1 h PG and 2 h PG levels, but not FPG or HbA1c levels. An elevated 1 h PG increased the estimated odds ratio of albuminuria more than three times in people with prediabetic 1 h PG (8.6-11.5 mmol/L: OR 3.60; 95% CI 1.70-7.64) and diabetic 1 h PG (≥11.6 mmol/L: OR 3.05; 95% CI 1.29-7.23). After adjusting for blood pressure and age, the association of elevated 1 h PG with albuminuria remained significant. Prediabetic or diabetic FPG, 2 h PG, or HbA1c did not have a statistically significant association with albuminuria. These findings suggest that 1 h PG seems to be the best glycemic parameter and is useful in recognizing persons with an elevated risk of early kidney disease due to hyperglycemia.