Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte to monocyte ratio and Systemic Inflammatory Index in sexually transmitted diseases.

Introduction: Hematologic biomarkers of inflammation may serve as valuable adjuncts in clinical practice, aiding in several aspects such as differential diagnosis, prognostic assessment for patient stratification and monitoring the efficacy of antimicrobial therapy. The aim of this study was to evaluate the efficacy of Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), Lymphocyte to Monocyte Ratio (LMR), and Systemic Inflammatory Index (SII) in predicting bacterial sexually transmitted infections (STI). Methods: This prospective study was conducted in the north-west region of Romania and included patients from several medical special units such as dermatology, obstetrics-gynecology, urology, and general practice. The study group comprised patients with a high suspicion of STI, while the control group consisted of healthy subjects. Quantitative data are presented as medians (interquartile ranges). Results: The median values of SII, NLR, and SIRI were higher in the group of subjects with sexually transmitted diseases compared to the control group [604.06 (432.36 - 880.02) vs. 556.89 (388.63 - 874.19); 2.61 (1.57 - 3.3) vs. 2.29 (1.66 - 3.26); and 0.95 (0.53 - 1.52) vs. 0.89 (0.67 - 1.34)]. Regarding PLR, the median values were lower in the group of subjects with sexually transmitted diseases compared to the control group [138.1 (99.19 - 169.6) vs. 140.65 (117 - 190.32)]. As for LMR, the median values were equal between the two groups [4.64 (3.74 - 6.11) vs. 4.64 (3.75 - 5.45)]. Nevertheless, the differences did not reach the significance level. Conclusion: Our study suggests that inflammatory biomarkers might aid in detecting bacterial STIs, but their significance was not statistically confirmed. Further research on alternative laboratory tests is needed for improved STI diagnosis and management.

BDNF-related mutations in major depressive disorder: a systematic review.

OBJECTIVE: A better understanding of the genetic, molecular and cellular mechanisms of brain-derived neurotrophic factor (BDNF) and its association with neuroplasticity could play a pivotal role in finding future therapeutic targets for novel drugs in major depressive disorder (MDD). Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD. METHODS: We conducted a keyword-guided search of the PubMed and Embase databases, using 'BDNF' or 'brain-derived neurotrophic factor' and 'major depressive disorder' and 'single-nucleotide polymorphism'. We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD. RESULTS: Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based on various demographic, clinico-phenotypical and neuromorphological variables. CONCLUSIONS: Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. Furthermore, biomarker approaches, specifically combinatory ones, involving BDNF should be further investigated.

Mental health difficulties and suicidal behaviours among young migrants: multicentre study of European adolescents.

BACKGROUND: Migration has been reported to be associated with higher prevalence of mental disorders and suicidal behaviour. AIMS: To examine the prevalence of emotional and behavioural difficulties, suicidal ideation and suicide attempts among migrant adolescents and their non-migrant peers. METHOD: A school-based survey was completed by 11 057 European adolescents as part of the Saving and Empowering Young Lives in Europe (SEYLE) study. RESULTS: A previous suicide attempt was reported by 386 (3.6%) adolescents. Compared with non-migrants, first-generation migrants had an elevated prevalence of suicide attempts (odds ratio (OR) 2.08; 95% CI 1.32-3.26; P=0.001 for European migrants and OR 1.86; 95% CI 1.06-3.27; P=0.031 for non-European migrants) and significantly higher levels of peer difficulties. Highest levels of conduct and hyperactivity problems were found among migrants of non-European origin. CONCLUSIONS: Appropriate mental health services and school-based supports are required to meet the complex needs of migrant adolescents. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Cognitive appraisal of exposure to specific types of trauma - a study of gender differences.

BACKGROUND: The role of gender in posttraumatic cognitions has increasingly been approached. The current study comparatively evaluates posttraumatic cognitions in men and women exposed to specific nonsexual trauma (motor vehicle accidents, work - related accidents, burns). METHODS: Posttraumatic cognitions and posttraumatic stress symptoms were comparatively assessed in 53 men and 37 women treated in 3 Romanian primary care units after specific accidental trauma. Posttraumatic Cognitions Inventory (PTCI) was used to assess posttraumatic cognitions, and the Short Post-Traumatic Stress Disorder Rating Interview (SPRINT) was used to assess posttraumatic stress symptoms. RESULTS: Men with significant posttraumatic stress symptoms endorsed more negative cognitions than women. Men with posttraumatic disability more consistently endorsed some negative cognitions regarding instrumentality, strength and control than their female counterparts. Women and men without posttraumatic disability reported similarly low levels of negative posttraumatic cognitions. Time elapsed since trauma increased most negative cognitions in men. CONCLUSIONS: The intensity of PTSD symptoms and presence of posttraumatic disability influence negative cognitions after exposure to accidental trauma. Women experiencing clinically significant PTSD symptoms endorse more cognitions regarding instrumentality, strength and control than male counterparts. Women with permanent disability after trauma report less cognitions involving emotionality, dependence and low self - efficacy than male counterparts. In the absence of permanent posttraumatic disability, men and women endorse similar levels of negative cognitions after accidental trauma. With time elapsed since trauma, men perceive decreasing self - efficacy, problem - solving and emotional control, while women perceive decreasing interpersonal cooperation. Despite limitations (cross-sectional design, lack of normative data for PTCI to ascertain culturally - specific gendered cognitions), this study supports the gender - sensitive approach of accidental trauma, especially when its consequences are pervasive, disabling and increasingly burdensome.

Physical activity in European adolescents and associations with anxiety, depression and well-being.

In this cross-sectional study, physical activity, sport participation and associations with well-being, anxiety and depressive symptoms were examined in a large representative sample of European adolescents. A school-based survey was completed by 11,110 adolescents from ten European countries who took part in the SEYLE (Saving and Empowering Young Lives in Europe) study. The questionnaire included items assessing physical activity, sport participation and validated instruments assessing well-being (WHO-5), depressive symptoms (BDI-II) and anxiety (SAS). Multi-level mixed effects linear regression was used to examine associations between physical activity/sport participation and mental health measures. A minority of the sample (17.9 % of boys and 10.7 % of girls; p < 0.0005) reported sufficient activity based on WHO guidelines (60 min + daily). The mean number of days of at least 60 min of moderate-to-vigorous activity in the past 2 weeks was 7.5 ± 4.4 among boys and 5.9 days ± 4.3 among girls. Frequency of activity was positively correlated with well-being and negatively correlated with both anxiety and depressive symptoms, up to a threshold of moderate frequency of activity. In a multi-level mixed effects model more frequent physical activity and participation in sport were both found to independently contribute to greater well-being and lower levels of anxiety and depressive symptoms in both sexes. Increasing activity levels and sports participation among the least active young people should be a target of community and school-based interventions to promote well-being. There does not appear to be an additional benefit to mental health associated with meeting the WHO-recommended levels of activity.

The relevance of personality assessment in estimating the risk of onset and the outcome of major depressive disorder.

In the past two decades, numerous studies have focused on the relationship between the psychobiological model of temperament and character and the development and evolution of major depressive disorder. This interest has been generated primarily because this particular model was developed as a tool for a comprehensive diagnosis of mental disorders. Such a diagnosis model, based on fewer diagnostic categories and a more phenomenological and person oriented approach seems to be supported by more recent research. The aim of this paper was to review the latest developments in this area, but in the context of the initial development of the psychobiological model of temperament and character, i.e. as a tool for the comprehensive diagnosis of depressed individuals. Data published so far supports the following observations: (1) high harm avoidance and low self-directedness are risk factors for the development of major depressive disorder, but further research is needed to clearly establish the role of the other dimensions or their facets as predictors for the development of a depressive episode; (2) although some evidence has been obtained so far regarding the use of harm avoidance, novelty seeking, reward dependence and cooperativeness in predicting treatment response in major depressive disorder, further research is needed to clarify and/or to replicate these findings; and (3) data on temperament and character dimensions related to relapse in major depressive disorder are insufficient, although some evidence has been brought to support the hypothesis that high harm avoidance scores, and low self-directedness and novelty seeking scores might serve as predictors; further prospective studies need to be carried out to establish their utility in this respect.

Pathological Internet Use and Risk-Behaviors among European Adolescents.

Risk-behaviors are a major contributor to the leading causes of morbidity among adolescents and young people; however, their association with pathological Internet use (PIU) is relatively unexplored, particularly within the European context. The main objective of this study is to investigate the association between risk-behaviors and PIU in European adolescents. This cross-sectional study was conducted within the framework of the FP7 European Union project: Saving and Empowering Young Lives in Europe (SEYLE). Data on adolescents were collected from randomized schools within study sites across eleven European countries. PIU was measured using Young's Diagnostic Questionnaire (YDQ). Risk-behaviors were assessed using questions procured from the Global School-Based Student Health Survey (GSHS). A total of 11,931 adolescents were included in the analyses: 43.4% male and 56.6% female (M/F: 5179/6752), with a mean age of 14.89 ± 0.87 years. Adolescents reporting poor sleeping habits and risk-taking actions showed the strongest associations with PIU, followed by tobacco use, poor nutrition and physical inactivity. Among adolescents in the PIU group, 89.9% were characterized as having multiple risk-behaviors. The significant association observed between PIU and risk-behaviors, combined with a high rate of co-occurrence, underlines the importance of considering PIU when screening, treating or preventing high-risk behaviors among adolescents.

Reading Books and Watching Films as a Protective Factor against Suicidal Ideation.

Reading books and watching films were investigated as protective factors for serious suicidal ideation (SSI) in young people with low perceived social belonging. Cross-sectional and longitudinal (12-month) analyses were performed using data from a representative European sample of 3256 students from the "Saving and Empowering Young Lives in Europe" study. Low social belonging was associated to SSI. However, reading books and watching films moderated this association, especially for those with lowest levels of belonging. This was true both at baseline and at 12 months of follow-up analyses. These media may act as sources of social support or mental health literacy and thus reduce the suicide risk constituted by low sense of belonging.

School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial.

BACKGROUND: Suicidal behaviours in adolescents are a major public health problem and evidence-based prevention programmes are greatly needed. We aimed to investigate the efficacy of school-based preventive interventions of suicidal behaviours. METHODS: The Saving and Empowering Young Lives in Europe (SEYLE) study is a multicentre, cluster-randomised controlled trial. The SEYLE sample consisted of 11,110 adolescent pupils, median age 15 years (IQR 14-15), recruited from 168 schools in ten European Union countries. We randomly assigned the schools to one of three interventions or a control group. The interventions were: (1) Question, Persuade, and Refer (QPR), a gatekeeper training module targeting teachers and other school personnel, (2) the Youth Aware of Mental Health Programme (YAM) targeting pupils, and (3) screening by professionals (ProfScreen) with referral of at-risk pupils. Each school was randomly assigned by random number generator to participate in one intervention (or control) group only and was unaware of the interventions undertaken in the other three trial groups. The primary outcome measure was the number of suicide attempt(s) made by 3 month and 12 month follow-up. Analysis included all pupils with data available at each timepoint, excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline. This study is registered with the German Clinical Trials Registry, number DRKS00000214. FINDINGS: Between Nov 1, 2009, and Dec 14, 2010, 168 schools (11,110 pupils) were randomly assigned to interventions (40 schools [2692 pupils] to QPR, 45 [2721] YAM, 43 [2764] ProfScreen, and 40 [2933] control). No significant differences between intervention groups and the control group were recorded at the 3 month follow-up. At the 12 month follow-up, YAM was associated with a significant reduction of incident suicide attempts (odds ratios [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and severe suicidal ideation (0·50, 0·27-0·92; p=0·025), compared with the control group. 14 pupils (0·70%) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 (1·51%) in the control group, and 15 pupils (0·75%) reported incident severe suicidal ideation in the YAM group versus 31 (1·37%) in the control group. No participants completed suicide during the study period. INTERPRETATION: YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents. These findings underline the benefit of this universal suicide preventive intervention in schools. FUNDING: Coordination Theme 1 (Health) of the European Union Seventh Framework Programme.

Pathological Internet use among European adolescents: psychopathology and self-destructive behaviours.

Rising global rates of pathological Internet use (PIU) and related psychological impairments have gained considerable attention in recent years. In an effort to acquire evidence-based knowledge of this relationship, the main objective of this study was to investigate the association between PIU, psychopathology and self-destructive behaviours among school-based adolescents in eleven European countries. This cross-sectional study was implemented within the framework of the European Union project: Saving and Empowering Young Lives in Europe. A representative sample of 11,356 school-based adolescents (M/F: 4,856/6,500; mean age: 14.9) was included in the analyses. PIU was assessed using the Young's Diagnostic Questionnaire. Psychopathology was measured using the Beck Depression Inventory-II, Zung Self-Rating Anxiety Scale and Strengths and Difficulties Questionnaire. Self-destructive behaviours were evaluated by the Deliberate Self-Harm Inventory and Paykel Suicide Scale. Results showed that suicidal behaviours (suicidal ideation and suicide attempts), depression, anxiety, conduct problems and hyperactivity/inattention were significant and independent predictors of PIU. The correlation between PIU, conduct problems and hyperactivity/inattention was stronger among females, while the link between PIU and symptoms of depression, anxiety and peer relationship problems was stronger among males. The association between PIU, psychopathology and self-destructive behaviours was stronger in countries with a higher prevalence of PIU and suicide rates. These findings ascertain that psychopathology and suicidal behaviours are strongly related to PIU. This association is significantly influenced by gender and country suggesting socio-cultural influences. At the clinical and public health levels, targeting PIU among adolescents in the early stages could potentially lead to improvements of psychological well-being and a reduction of suicidal behaviours.

Life-time prevalence and psychosocial correlates of adolescent direct self-injurious behavior: a comparative study of findings in 11 European countries.

OBJECTIVES: To investigate the prevalence and associated psychosocial factors of occasional and repetitive direct self-injurious behavior (D-SIB), such as self-cutting, -burning, -biting, -hitting, and skin damage by other methods, in representative adolescent samples from 11 European countries. METHODS: Cross-sectional assessment of adolescents was performed within the European Union funded project, Saving and Empowering Young Lives in Europe (SEYLE), which was conducted in 11 European countries. The representative sample comprised 12,068 adolescents (F/M: 6,717/5,351; mean age: 14.9 ± 0.89) recruited from randomly selected schools. Frequency of D-SIB was assessed by a modified 6-item questionnaire based on previously used versions of the Deliberate Self-Harm Inventory (DSHI). In addition, a broad range of demographic, social, and psychological factors was assessed. RESULTS: Overall lifetime prevalence of D-SIB was 27.6%; 19.7% reported occasional D-SIB and 7.8% repetitive D-SIB. Lifetime prevalence ranged from 17.1% to 38.6% across countries. Estonia, France, Germany, and Israel had the highest lifetime rates of D-SIB, while students from Hungary, Ireland, and Italy reported low rates. Suicidality as well as anxiety and depressive symptoms had the highest odds ratios for both occasional and repetitive D-SIB. There was a strong association of D-SIB with both psychopathology and risk-behaviors, including family related neglect and peer-related rejection/victimization. Associations between psychosocial variables and D-SIB were strongly influenced by both gender and country. Only a minor proportion of the adolescents who reported D-SIB ever received medical treatment. CONCLUSION: These results suggest high lifetime prevalence of D-SIB in European adolescents. Prevalence as well as psychosocial correlates seems to be significantly influenced by both gender and country. These results support the need for a multidimensional approach to better understand the development of SIB and facilitate culturally adapted prevention/intervention.

The saving and empowering young lives in Europe (SEYLE) randomized controlled trial (RCT): methodological issues and participant characteristics.

BACKGROUND: Mental health problems and risk behaviours among young people are of great public health concern. Consequently, within the VII Framework Programme, the European Commission funded the Saving and Empowering Young Lives in Europe (SEYLE) project. This Randomized Controlled Trial (RCT) was conducted in eleven European countries, with Sweden as the coordinating centre, and was designed to identify an effective way to promote mental health and reduce suicidality and risk taking behaviours among adolescents. OBJECTIVE: To describe the methodological and field procedures in the SEYLE RCT among adolescents, as well as to present the main characteristics of the recruited sample. METHODS: Analyses were conducted to determine: 1) representativeness of study sites compared to respective national data; 2) response rate of schools and pupils, drop-out rates from baseline to 3 and 12 month follow-up, 3) comparability of samples among the four Intervention Arms; 4) properties of the standard scales employed: Beck Depression Inventory, Second Edition (BDI-II), Zung Self-Rating Anxiety Scale (Z-SAS), Strengths and Difficulties Questionnaire (SDQ), World Health Organization Well-Being Scale (WHO-5). RESULTS: Participants at baseline comprised 12,395 adolescents (M/F: 5,529/6,799; mean age=14.9±0.9) from Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain. At the 3 and 12 months follow up, participation rates were 87.3% and 79.4%, respectively. Demographic characteristics of participating sites were found to be reasonably representative of their respective national population. Overall response rate of schools was 67.8%. All scales utilised in the study had good to very good internal reliability, as measured by Cronbach's alpha (BDI-II: 0.864; Z-SAS: 0.805; SDQ: 0.740; WHO-5: 0.799). CONCLUSIONS: SEYLE achieved its objective of recruiting a large representative sample of adolescents within participating European countries. Analysis of SEYLE data will shed light on the effectiveness of important interventions aimed at improving adolescent mental health and well-being, reducing risk-taking and self-destructive behaviour and preventing suicidality. TRIAL REGISTRATION: US National Institute of Health (NIH) clinical trial registry (NCT00906620) and the German Clinical Trials Register (DRKS00000214).

Psychiatric Adverse Effects Of Interferon Therapy.

A number of data support the involvement of immunological mechanisms in the etiology of psychiatric disorders. The nervous and immune systems are physiologically integrated and influence each other's functioning. Clinical studies have reported a larger number of psychiatric symptoms consecutive to immunomodulating interferon therapy. The most frequent are depression, suicidal behavior, manic syndrome, anxiety disorders, psychotic disorders and delirium associated with an array of unspecific psychiatric symptoms: fatigue, irritability, psycho-motor retardation, decreased libido, insomnia, concentration difficulties and attention deficit. Another undesired consequence of interferon therapy is the worsening of a preexistent psychiatric disorder. Thus, a history of psychiatric disorder is currently one of the contraindications of interferon therapy. Psychiatric adverse events may occur either shortly after the initiation of therapy, or as a result of ongoing treatment, but most adverse events occur after 3 weeks of treatment. Although there are relatively few studies on statistically significant patient samples, current data underline the importance of managing these effects and also the most indicated treatment strategies. Therefore, an improved psychiatric management of these adverse effects may change the gastroenterologist's decision to exclude from treatment high - risk patient categories such as those with mood disorders, alcohol or drug abuse, or other addiction.

Saving and empowering young lives in Europe (SEYLE): a randomized controlled trial.

BACKGROUND: There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people's mental health.The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. METHODS AND DESIGN: The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR), awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. DISCUSSION: Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior, well-documented and randomized studies are lacking. The effects of such interventions in terms of combating unhealthy lifestyles in young people, which often characterize suicidal individuals, have never been reported. We know that unhealthy and risk-taking behaviors are detrimental to individuals' current and future health. It is, therefore, crucial to test well-designed, longitudinal mental health-promoting and suicide-preventive interventions by evaluating the implications of such activities for reducing unhealthy and risk behaviors while concurrently promoting healthy ones. TRIAL REGISTRATION: The German Clinical Trials Register, DRKS00000214.

Paraoxonase 1 activities and polymorphisms in autism spectrum disorders.

Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of conditions of unknown aetiology, characterized by significant disturbances in social, communicative and behavioural functioning. Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype.

High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism.

Autism is a behaviorally defined disorder of unknown etiology that is thought to be influenced by genetic and environmental factors. High levels of homocysteine and oxidative stress are generally associated with neuropsychiatric disorders. The purpose of this study was to compare the level of homocysteine and other biomarkers in children with autism to corresponding values in age-matched healthy children. We measured total homocysteine (tHcy), vitamin B(12), paraoxonase and arylesterase activities of human paraoxonase 1 (PON1) in plasma and glutathione peroxidase (GPx) activity in erythrocytes from 21 children: 12 with autism (age: 8.29 +/- 2.76 years) and 9 controls (age: 8.33 +/- 1.82 years). We found statistically significant differences in tHcy levels and in arylesterase activity of PON1 in children with autism compared to the control group: 9.83 +/- 2.75 vs. 7.51 +/- 0.93 micromol/L (P < or =0.01) and 72.57 +/- 11.73 vs. 81.83 +/- 7.39 kU/L (P < or =0.005). In the autistic group there was a strong negative correlation between tHcy and GPx activity and the vitamin B(12) level was low or suboptimal. In conclusion, our study shows that in children with autism there are higher levels of tHcy, which is negatively correlated with GPx activity, low PON1 arylesterase activity and suboptimal levels of vitamin B(12).