Sex Steroid Hormone Analysis in Human Tear Fluid Using a Liquid Chromatography—Mass Spectrometry Method

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography–tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC–MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases

The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration

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Cumulative contextual risk at birth in relation to adolescent substance use, conduct problems, and risky sex: General and specific predictive associations in a Finnish birth cohort

Background—Research indicates that risk factors cluster in the most vulnerable youth, increasing their susceptibility for adverse developmental outcomes. However, most studies of cumulative risk are cross-sectional or short-term longitudinal, and have been based on data from the United States or the United Kingdom. Using data from the Northern Finland Birth Cohort 1986 Study (NFBC1986), we examined cumulative contextual risk (CCR) at birth as a predictor of adolescent substance use and co-occurring conduct problems and risky sex to determine the degree to which CCR predicts specific outcomes over-and-above its effect on general problem behavior, while testing for moderation of associations by gender. Methods—Analyses of survey data from 6963 participants of the NFBC1986 followed from the prenatal/birth period into adolescence were conducted using structural equation modeling. Results—CCR had long-term positive associations with first-order substance use, conduct problems, and risky sex factors, and, in a separate analysis, with a second-order general problem behavior factor. Further analyses showed that there was a positive specific effect of CCR on risky sex, over-and-above general problem behavior, for girls only. Conclusions—This study, conducted within the Finnish context, showed that CCR at birth had long-term general and specific predictive associations with substance use and co-occurring problem behaviors in adolescence; effects on risky sex were stronger for girls. Results are consistent with the hypothesis that early exposure to CCR can have lasting adverse consequences, suggesting the need for early identification and intervention efforts for vulnerable children

Cumulative contextual risk at birth in relation to adolescent substance use, conduct problems, and risky sex: General and specific predictive associations in a Finnish birth cohort

Background—Research indicates that risk factors cluster in the most vulnerable youth, increasing their susceptibility for adverse developmental outcomes. However, most studies of cumulative risk are cross-sectional or short-term longitudinal, and have been based on data from the United States or the United Kingdom. Using data from the Northern Finland Birth Cohort 1986 Study (NFBC1986), we examined cumulative contextual risk (CCR) at birth as a predictor of adolescent substance use and co-occurring conduct problems and risky sex to determine the degree to which CCR predicts specific outcomes over-and-above its effect on general problem behavior, while testing for moderation of associations by gender. Methods—Analyses of survey data from 6963 participants of the NFBC1986 followed from the prenatal/birth period into adolescence were conducted using structural equation modeling. Results—CCR had long-term positive associations with first-order substance use, conduct problems, and risky sex factors, and, in a separate analysis, with a second-order general problem behavior factor. Further analyses showed that there was a positive specific effect of CCR on risky sex, over-and-above general problem behavior, for girls only. Conclusions—This study, conducted within the Finnish context, showed that CCR at birth had long-term general and specific predictive associations with substance use and co-occurring problem behaviors in adolescence; effects on risky sex were stronger for girls. Results are consistent with the hypothesis that early exposure to CCR can have lasting adverse consequences, suggesting the need for early identification and intervention efforts for vulnerable children

The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension : a cross-sectional study

Background: Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. Methods: The 541 participants (20–72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. Results: Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models). Conclusion: Higher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension. Trial registration: ClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).publishedVersionPeer reviewe

Psychosis among "healthy" siblings of schizophrenia patients

BACKGROUND: Schizophrenia aggregates in families and accurate diagnoses are essential for genetic studies of schizophrenia. In this study, we investigated whether siblings of patients with schizophrenia can be identified as free of any psychotic disorder using only register information. We also analyzed the emergence of psychotic disorders among siblings of patients with schizophrenia during seven to eleven years of follow-up. METHODS: A genetically homogenous population isolate in north-eastern Finland having 365 families with 446 patients with a diagnosis of schizophrenia was initially identified in 1991 using four nationwide registers. Between 1998 and 2002, 124 patients and 183 siblings in 110 families were contacted and interviewed using SCID-I, SCID-II and SANS. We also compared the frequency of mental disorders between siblings and a random population comparison group sample. RESULTS: Thirty (16%) siblings received a diagnosis of psychotic disorder in the interview. 14 siblings had had psychotic symptoms already before 1991, while 16 developed psychotic symptoms during the follow-up. Over half of the siblings (n = 99, 54%) had a lifetime diagnosis of any mental disorder in the interview. CONCLUSION: Register information cannot be used to exclude psychotic disorders among siblings of patients with schizophrenia. The high rate of emergence of new psychotic disorders among initially healthy siblings should be taken into account in genetic analysis

Different vulnerability indicators for psychosis and their neuropsychological characteristics in the Northern Finland 1986 Birth Cohor

This study is one of very few that has investigated the neuropsychological functioning of both familial and clinical high risk subjects for psychosis. Participants (N = 164) were members of the Northern Finland 1986 Birth Cohort in the following four groups: familial risk for psychosis (n = 62), clinical risk for psychosis (n = 20), psychosis (n = 13), and control subjects (n = 69). The neurocognitive performance of these groups was compared across 19 cognitive variables. The two risk groups did not differ significantly from controls, but differed from the psychosis group in fine motor function. Neuropsychological impairments were not evident in a non-help-seeking high-risk sample

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens