Differences by sex and gender in the association between minority stress and alcohol use among sexual and gender minority youth: A daily diary study.

RATIONALE: Sexual and gender minority (SGM) youth consume more alcohol than their heterosexual, cisgender peers. The experience of minority stress is theorized to explain these disparities. Research often neglects the day-to-day variability in minority stress that SGM youth encounter and whether alcohol use is associated with daily experiences of minority stress. Further, there is heterogeneity in alcohol use among SGM youth. Sex assigned at birth and gender identity could potentially explain this heterogeneity. OBJECTIVE: Therefore, this study aimed to examine whether daily experiences of minority stress were associated with daily alcohol use among SGM youth and how these associations differed by sex assigned at birth and gender identity. METHODS: A 14-day daily diary study was conducted among 393 Dutch SGM youth (M age = 18.36 SD = 2.65). RESULTS: Results showed few significant associations between both mean levels of minority stress and daily experiences with minority stress with alcohol use. However, higher mean levels of prejudice events were associated with higher odds of daily alcohol use (OR = 7.01, 95% CI: 1.20-40.89). Daily experiences with identity concealment were associated with lower odds of daily alcohol use for males (OR = 0.72, 95% CI: 0.60-0.86), but not for females (OR = 1.11, 95% CI: 0.93-1.32). Further, for cisgender youth, daily experiences with prejudice events were associated with higher odds of alcohol use (OR = 1.99, 95% CI: 1.05-3.78), but this was not the case for gender minority youth (OR = 0.42, 95% CI: 0.15-1.18). CONCLUSIONS: The findings showed few significant associations between minority stressors and alcohol use, but daily experiences of concealment and prejudice events were associated with daily alcohol use and these associations varied by sex assigned at birth and gender identity, respectively.

Differences in Adolescents' Alcohol Use and Smoking Behavior between Educational Tracks: Do Popularity Norms Matter?

Explanations about differences in drinking and smoking rates between educational tracks have so far mainly focused on factors outside the classroom. The extent to which these behaviors are rewarded with popularity within a classroom-so called popularity norms-and their interaction with individual characteristics could explain the observed differences in risk behavior. 1860 adolescents (Mage = 13.04; 50% girls) from 81 different classrooms reported three times during one academic year about their own and their classmates behavior. Overall, in vocational tracks popularity norms for alcohol and smoking were more positive and predicted classroom differences in alcohol and smoking. Knowledge about classroom processes can advance the field in unraveling the functional aspects of risk behavior in adolescence. Preregistration: The hypotheses and the analytical plan of this study were preregistered under number #39136 ( https://aspredicted.org/blind.php?x=gx77p6 ).

Effectiveness of a Tailored Work-Related Support Intervention for Patients Diagnosed with Gastrointestinal Cancer: A Multicenter Randomized Controlled Trial.

Purpose The aim of this research was to study the effectiveness on return to work (RTW) of an early tailored work-related support intervention in patients diagnosed with curative gastrointestinal cancer. Methods A multicenter randomized controlled trial was undertaken, in which patients were assigned randomly to the intervention or the control group (usual care). The intervention encompassed three psychosocial work-related support meetings, starting before treatment. Five self-reported questionnaires were sent over twelve months of follow-up. Primary outcome was days until RTW (fulltime or partial) and secondary outcomes included work status, quality of life, work ability, and work limitations. Descriptive analysis, Kaplan-Meier analysis, relative risk ratio and linear mixed models were applied. Results Participants (N = 88) had a mean age of 55 years; 67% were male and the most common cancer type was colon cancer (66%). Of the participants, 42 were randomized to the intervention group. The median time from sick leave until RTW was 233 days (range 187-279 days) for the control group, versus 190 days (range 139-240 days) for the intervention group (log-rank p = 0.37). The RTW rate at twelve months after baseline was 83.3% for the intervention group and 73.5% for the control group. Work limitations did statistically differ between the groups over time (p = 0.01), but quality of life and work ability did not. Conclusion Patients in the intervention group seem to take fewer days to RTW, albeit not to a statistically significant extent.Trial registration Trial NL4920 (NTR5022) (Dutch Trial Register https://www.trialregister.nl ).

Beyond not bad or just okay: social predictors of young adults' wellbeing and functioning (a TRAILS study).

BACKGROUND: Various childhood social experiences have been reported to predict adult outcomes. However, it is unclear how different social contexts may influence each other's effects in the long run. This study examined the joint contribution of adolescent family and peer experiences to young adult wellbeing and functioning. METHODS: Participants came from the TRacking Adolescents' Individual Lives Survey (TRAILS) study (n = 2230). We measured family and peer relations at ages 11 and 16 (i.e. family functioning, perceived parenting, peer status, peer relationship quality), and functioning as the combination of subjective wellbeing, physical and mental health, and socio-academic functioning at age 22. Using structural equation modelling, overall functioning was indicated by two latent variables for positive and negative functioning. Positive, negative and overall functioning at young adulthood were regressed on adolescent family experiences, peer experiences and interactions between the two. RESULTS: Family experiences during early and mid-adolescence were most predictive for later functioning; peer experiences did not independently predict functioning. Interactions between family and peer experiences showed that both protective and risk factors can have context-dependent effects, being exacerbated or overshadowed by negative experiences or buffered by positive experiences in other contexts. Overall the effect sizes were modest at best. CONCLUSIONS: Adolescent family relations as well as the interplay with peer experiences predict young adult functioning. This emphasizes the importance of considering the relative effects of one context in relation to the other.

Functional outcomes of child and adolescent mental disorders. Current disorder most important but psychiatric history matters as well.

BACKGROUND: Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes. METHOD: We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use). RESULTS: Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder. CONCLUSION: To understand current functioning, it is necessary to examine both current and past psychiatric status.

Mental health in Dutch adolescents: a TRAILS report on prevalence, severity, age of onset, continuity and co-morbidity of DSM disorders.

BACKGROUND: With psychopathology rising during adolescence and evidence suggesting that adult mental health burden is often due to disorders beginning in youth, it is important to investigate the epidemiology of adolescent mental disorders. METHOD: We analysed data gathered at ages 11 (baseline) and 19 years from the population-based Dutch TRacking Adolescents' Individual Lives Survey (TRAILS) study. At baseline we administered the Achenbach measures (Child Behavior Checklist, Youth Self-Report) and at age 19 years the World Health Organization's Composite International Diagnostic Interview version 3.0 (CIDI 3.0) to 1584 youths. RESULTS: Lifetime, 12-month and 30-day prevalences of any CIDI-DSM-IV disorder were 45, 31 and 15%, respectively. Half were severe. Anxiety disorders were the most common but the least severe whereas mood and behaviour disorders were less prevalent but more severe. Disorders persisted, mostly by recurrence in mood disorders and chronicity in anxiety disorders. Median onset age varied substantially across disorders. Having one disorder increased subjects' risk of developing another disorder. We found substantial homotypic and heterotypic continuity. Baseline problems predicted the development of diagnosable disorders in adolescence. Non-intact families and low maternal education predicted externalizing disorders. Most morbidity concentrated in 5-10% of the sample, experiencing 34-55% of all severe lifetime disorders. CONCLUSIONS: At late adolescence, 22% of youths have experienced a severe episode and 23% only mild episodes. This psychopathology is rather persistent, mostly due to recurrence, showing both monotypic and heterotypic continuity, with family context affecting particularly externalizing disorders. High problem levels at age 11 years are modest precursors of incident adolescent disorders. The burden of mental illness concentrates in 5-10% of the adolescent population.

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Effects of structural and dynamic family characteristics on the development of depressive and aggressive problems during adolescence. The TRAILS study.

Both structural (i.e., SES, familial psychopathology, family composition) and dynamic (i.e., parental warmth and rejection) family characteristics have been associated with aggressive and depressive problem development. However, it is unclear to what extent (changes in) dynamic family characteristics have an independent effect on problem development while accounting for stable family characteristics and comorbid problem development. This issue was addressed by studying problem development in a large community sample (N = 2,230; age 10-20) of adolescents using Linear Mixed models. Paternal and maternal warmth and rejection were assessed via the Egna Minnen Beträffande Uppfostran for Children (EMBU-C). Aggressive and depressive problems were assessed via subscales of the Youth/Adult Self-Report. Results showed that dynamic family characteristics independently affected the development of aggressive problems. Moreover, maternal rejection in preadolescence and increases in paternal rejection were associated with aggressive problems, whereas decreases in maternal rejection were associated with decreases in depressive problems over time. Paternal and maternal warmth in preadolescence was associated with fewer depressive problems during adolescence. Moreover, increases in paternal warmth were associated with fewer depressive problems over time. Aggressive problems were a stable predictor of depressive problems over time. Finally, those who increased in depressive problems became more aggressive during adolescence, whereas those who decreased in depressive problems became also less aggressive. Besides the effect of comorbid problems, problem development is to a large extent due to dynamic family characteristics, and in particular to changes in parental rejection, which leaves much room for parenting-based interventions.

Acute stress-related gastrointestinal ischemia.

We report a case of acute gastrointestinal ischemia during a very stressful event in whom the diagnosis was made by 24-hour tonometry. This case report unequivocally links a stressful event with increased catecholamine release and subsequent severe symptomatic gastrointestinal ischemia. The role of ischemia as potential pathophysiological mechanism has never been studied in detail. The clinical significance of finding such an association is underscored by this case report, where a vasoactive drug normally used for hypertension treatment resulted in greatly improved abdominal symptoms.

Disruptive behaviors and HPA-axis activity in young adolescent boys and girls from the general population.

It is important to investigate associations between biological factors and disruptive behaviors in children and adolescents. Antisocial, aggressive, and criminal behaviors in adults often begin early in life. Disruptive behaviors are often thought to be associated with low activity of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol, the end-product of this axis, can be measured to investigate HPA-axis activity. Previous studies on this topic concerned clinical or high risk samples. The aim of the present study was to investigate to which extent HPA-axis functioning plays a role in disruptive behaviors in pre-adolescents from the general population. One thousand seven hundred and sixty eight 10- to 12-year-olds from the Dutch general population were investigated. Disruptive behaviors were assessed with the Child Behavior Checklist, the Youth Self-Report, and the Antisocial Behavior Questionnaire. Baseline morning and evening salivary cortisol levels were assessed. Unexpectedly, small associations were found between disruptive behaviors, including attention problems, and higher cortisol levels. However, all effect sizes of significant effects were very small. Our study indicated that HPA-axis functioning may be more relevant in clinical or high risk samples than at the general population level. The association between HPA-axis functioning and attention problems, that has gotten less attention than that with aggressive or delinquent behaviors, requires further research. Furthermore, because effect sizes were relatively small, it can be concluded that, in pre-adolescence, the measures of baseline HPA-axis functioning that were used for the present study can not be used as biological markers for disruptive behaviors.

Internalizing and externalizing problems in adolescence: general and dimension-specific effects of familial loadings and preadolescent temperament traits.

BACKGROUND: We investigated the links between familial loading, preadolescent temperament, and internalizing and externalizing problems in adolescence, hereby distinguishing effects on maladjustment in general versus dimension-specific effects on either internalizing or externalizing problems. METHOD: In a population-based sample of 2230 preadolescents (10-11 years) familial loading (parental lifetime psychopathology) and offspring temperament were assessed at baseline by parent report, and offspring psychopathology at 2.5-years follow-up by self-report, teacher report and parent report. We used purified measures of temperament and psychopathology and partialled out shared variance between internalizing and externalizing problems. RESULTS: Familial loading of internalizing psychopathology predicted offspring internalizing but not externalizing problems, whereas familial loading of externalizing psychopathology predicted offspring externalizing but not internalizing problems. Both familial loadings were associated with Frustration, low Effortful Control, and Fear. Frustration acted as a general risk factor predicting severity of maladjustment; low Effortful Control and Fear acted as dimension-specific risk factors that predicted a particular type of psychopathology; whereas Shyness, High-Intensity Pleasure, and Affiliation acted as direction markers that steered the conditional probability of internalizing versus externalizing problems, in the event of maladjustment. Temperament traits mediated one-third of the association between familial loading and psychopathology. Findings were robust across different composite measures of psychopathology, and applied to girls as well as boys. CONCLUSIONS: With regard to familial loading and temperament, it is important to distinguish general risk factors (Frustration) from dimension-specific risk factors (familial loadings, Effortful Control, Fear), and direction markers that act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from both types of risk factors. About one-third of familial loading effects on psychopathology in early adolescence are mediated by temperament.

Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions.

The rat connexin40 gap junction channel is permeable to monovalent cations including tetramethylammonium and tetraethylammonium ions. Larger tetraalkyammonium (TAA(+)) ions beginning with tetrabutylammonium (TBA(+)) reduced KCl junctional currents disproportionately. Ionic blockade by tetrapentylammonium (TPeA(+)) and tetrahexylammonium (THxA(+)) ions were concentration- and voltage-dependent and occurred only when TAA(+) ions were on the same side as net K(+) efflux across the junction, indicative of block of the ionic permeation pathway. The voltage-dependent dissociation constants (K(m)(V(j))) were lower for THxA(+) than TPeA(+), consistent with steric effects within the pore. The K(m)-V(j) relationships for TPeA(+) and THxA(+) were fit with different reaction rate models for a symmetrical (homotypic) connexin gap junction channel and were described by either a one- or two-site model that assumed each ion traversed the entire V(j) field. Bilateral addition of TPeA(+) ions confirmed a common site of interaction within the pore that possessed identical K(m)(V(j)) values for cis-trans concentrations of TPeA(+) ions as indicated by the modeled I-V relations and rapid channel block that precluded unitary current measurements. The TAA(+) block of K(+) currents and bilateral TPeA(+) interactions did not alter V(j)-gating of Cx40 gap junctions. N-octyl-tributylammonium and -triethylammonium also blocked rCx40 channels with higher affinity and faster kinetics than TBA(+) or TPeA(+), indicative of a hydrophobic site within the pore near the site of block.

An SV40 large T-antigen immortalized human umbilical vein endothelial cell line for anti-endothelial cell antibody detection.

OBJECTIVE: Anti-endothelial cell antibodies in serum of patients with different inflammatory diseases can be detected by a whole cell enzyme-linked immunosorbant assay, using primary cultures of human umbilical vein endothelial cells. To avoid repeated isolation, it would be of great value if an immortal endothelial cell line could be used to perform anti-endothelial cell antibody assays. METHODS: In this study endothelial cells from human umbilical and iliac veins and arteries were transfected with a plasmid containing the Simian Virus 40 large T-antigen. Endothelial cell line(s) derived from this procedure were compared with human umbilical vein endothelial cells in the anti-endothelial cell antibody assay. RESULTS: After transfection, clones of homologous cell populations showed an extended lifespan, before entering a period of crisis. In one human umbilical vein endothelial cell clone a subpopulation of cells escaped crisis and became immortal (EVLC2). Telomerase was activated in this endothelial cell line, resulting in maintenance of the telomere length. There was a significant correlation between anti-endothelial cell antibody testing on human umbilical vein endothelial cells and on the cell line EVLC2. CONCLUSION: The Simian Virus 40 large T-antigen immortalized human umbilical vein endothelial cell line EVLC2 may be useful for the detection of anti-endothelial cell antibodies.

Voltage clamp limitations of dual whole-cell gap junction current and voltage recordings. I. Conductance measurements.

Previous correction methods for series access resistance errors in the dual whole-cell configuration did not take into account the effect of nonzero resting potentials (E(rest)) and junctional reversal potentials (E(rev)). Dual whole-cell currents were modeled according to resistor-circuit analysis and two correction formulas for the measurement of junctional currents (I(j)) were assessed. The equations for I(j), derived from Kirchoff's law before and after baseline subtraction of the nonjunctional current, were assessed for accuracy under a variety of whole-cell patch-clamp recording conditions. Both equations accurately correct for dual whole-cell voltage-clamp errors provided that the cellular parameters are included in the nonbaseline subtracted I(j) derivations. Junctional conductance (g(j)) estimates are most reliable at high junctional resistance (R(j)) values and minimize the need for corrective methods based on electrode series and cellular input resistances (R(el) and R(in)). In the "open-cell" configuration, low R(j) values relative to R(in) are required for accurate g(j) estimates. These methods provide the basis for accurate quantitative measurements of junctional resistance (or conductance) of gap junction channels or connexin hemichannels in the dual whole-cell or open-cell configurations. Revaluation of V(j)-dependent gating of rat connexin40 g(j) produced nearly identical Boltzmann fits to previously published data. Continuous g(j)-V(j) curves generated by variable slope V(j) ramps provide for more accurate fits and assessment of the time-dependence of the half-inactivation voltage and net gating charge movement.