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Objective: This study compared public attributions and attitudes toward adult and child depression, with a focus on problem recognition, medical and social causes, help-seeking recommendations, perceptions of violence, and the use of coercion.Methods: The investigators compared data from two special modules of the 1996 and 2002 nationally representative General Social Survey on public response to mental illness. Respondents answered questions regarding a vignette in which an adult had depression (N=193) or one in which a child had depression (N=312).Results: Respondents evaluated childhood depression as more serious than adult depression (83% versus 51%, respectively) and saw a greater potential for violence toward others among children with depression (40% for children versus 30% for adults). More respondents endorsed treatment of all types, including coerced care, for children with depression. However, significantly fewer recommended talking to family and friends about a child's mental health problem.Conclusions: Americans are more concerned about children's depression than adults' depression and reveal more prejudice regarding perceptions of dangerousness. More respondents endorsed formal care than informal care and advice. However, the heightened stigma surrounding childhood depression poses unique challenges for youths with depression and their families. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to understand the level of public knowledge about attention-deficit hyperactivity disorder (ADHD), treatment preferences for the disorder, and their sociodemographic correlates.Methods: A short battery of questions about ADHD was included in the 2002 General Social Survey (N=1,139). In face-to-face interviews, respondents answered questions about whether they had heard of ADHD, what they knew about ADHD, their beliefs about whether ADHD is a "real" disease, and opinions about whether children with ADHD should be offered counseling or medication.Results: Just under two-thirds of respondents (64%) had heard of ADHD; most could not provide detailed information about the disorder. Women and those with higher levels of education were more likely to have heard of ADHD; African Americans, members of other nonwhite racial and ethnic groups, and older respondents were less likely to have heard of ADHD. Among respondents who had heard of ADHD, 78% said they believed ADHD to be a real disease; women, white respondents, and persons with higher income most often endorsed that belief. Most respondents (65%) endorsed the use of both counseling and medication, although counseling was endorsed as a sole treatment more often than medication. There were few sociodemographic differences in treatment preferences.Conclusions: The public is not well informed about ADHD. Future media and educational efforts should seek to provide accurate information about ADHD, with a special effort to reach specific populations such as men, nonwhite minority groups, and older Americans. [ABSTRACT FROM AUTHOR]

Students with "invisible" disabilities-including autism spectrum disorder (ASD), attention deficit disorder (ADD/ADHD), learning disorders, and mental health conditions-make up an increasingly large share of college students in the United States. Despite these gains in access, students with invisible disabilities remain disadvantaged relative to their neurotypical and non-disabled peers in many parts of the college experience, including academically. Researchers have hypothesized that inequalities in pre-college academic preparation, barriers to social integration, and lower levels of engagement on college campuses may be at least partially to blame. We test this hypothesis using newly available survey data on college students in the state of Indiana (n = 2728). Based on a series of decompositions, we show that students with invisible disabilities face a series of interrelated challenges, beginning with their academic preparation and extending into their social and academic experiences on college campuses. That these disadvantages feed into one another suggests the presence of a cumulative advantage/disadvantage process, in which early advantages and disadvantages compound as disabled and non-disabled students move through the educational system., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study evaluated the association of autistic traits (RAADS-14) with academic and social outcomes among college students using data from an online survey (N = 2,736). In the academic domain, the total trait score and all subscale scores (mentalizing deficits, social anxiety, sensory reactivity) were associated with course failure and academic difficulties independent of an autism diagnosis; the total score and mentalizing deficits also predicted lower grade point average (GPA). In the social domain, the total trait score and subscale scores were associated with lower odds of having a confidant, lower friendship quality, and higher odds of social exclusion. Subgroup analyses revealed that autistic traits had more consistently negative associations with social outcomes for students without an autism diagnosis than for students with a diagnosis. Associations were also more often significant for women than men. These results support the development of programs and services for students with autistic traits regardless of diagnostic status., (© 2022. The Author(s).)

This study examines the implications of the coronavirus pandemic for college students' health and education, with special attention to variation by disability status. Disaster research supports the hypothesis that students with disabilities will experience higher-than-usual levels of pandemic-related stress, which could lead to re-evaluations of their educational expectations and declines in health. We evaluate this hypothesis by modeling changes in students' (1) mental and physical health and (2) educational expectations during the first year (spring of 2020 to spring of 2021) of the pandemic, using survey data collected from a population-based sample of college students in the state of Indiana. Although we observe across-the-board declines in both domains, students with disabilities were especially vulnerable. Mediation analyses suggest that differential exposure to financial and illness-related stressors is partially to blame, explaining a significant portion of the group differences between students with and without disabilities. We interpret these results as evidence of the unique vulnerabilities associated with disability status and its wide-ranging importance as a dimension of social stratification., (© 2022 The Authors.)

Lay Abstract: Studies have shown that children and older adults on the autism spectrum experience more physical and mental health problems than their neurotypical peers. Less is known about the physical and mental health of college students on the spectrum. Studying college students is important because young adults on the spectrum are enrolling in college at increasing rates and because health problems can be a barrier to succeeding in college. We collected data from 2820 students at 14 colleges and universities using an online survey, some of whom had registered for accommodations based on autism and others of whom had not. We used the data to compare the physical and mental health of students on the spectrum to their neurotypical peers. Because students with autism often report other disabilities that also affect health, we accounted for whether they experienced a learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or any other disabilities. We assessed health using self-reports of how healthy they were physically and mentally, and reports of depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. We found that students with autism reported poorer physical and mental health, more depressive symptoms, and more symptoms of anxiety even after taking into account other disabilities they may have experienced. They were also less likely to report sleep deprivation and binge drinking. Our results argue for developing specialized services to address the physical and mental health challenges of college students on the spectrum.

This study describes the academic, social, and health experiences of college students on the autism spectrum as they compare to students with other disabilities and their non-disabled, neurotypical peers. Data were from an online survey of college students at 14 public institutions (N = 3073). There were few significant differences between students on the spectrum and students with other disabilities. Both groups of students reported significantly worse outcomes than neurotypical students on academic performance, social relationships and bullying, and physical and mental health. The findings suggest that some of the challenges students on the spectrum face in college result from the stigma and social rejection associated with disability rather than from the unique characteristics of autism.

We used data from the 2011 Survey of Pathways to Diagnosis and Services (N = 1,420) to evaluate a conceptual model linking social background (race-ethnicity, socioeconomic status [SES]) to parental distress through children's clinical profiles and parental beliefs about the nature and causes of their child's autism. Children's clinical profiles varied by social background; white children and children of more highly educated and affluent parents were less likely to experience comorbid conditions and were more likely to be diagnosed with Asperger's. Parental beliefs also varied such that parents of racial-ethnic minority children and parents of lower SES perceived their child's condition as more uncertain and were less likely to attribute it to genetic causes. Parents of Hispanic children and with lower incomes were more likely to be upset by the child's condition. Although parental beliefs had independent associations with distress, children's clinical profiles contributed more to explaining variation in distress.

The adoption of process intensification to anaerobic digestion can present significant complications for digester mixing and process performance. This work investigated how increasing the solids concentration of the digester sludge influenced the process at various mixing energy inputs. Based on the results, adequate mixing is defined qualitatively as the input of sufficient energy to mobilize the reactor contents without producing significant regions of inhibitory shear force. However, the quantitative definition is dependent on the solids concentration of the sludge. But, the existing design criterion of specific mixing power input based on fluid volume (W/m 3 ) does not represent it well. Therefore, a new design criterion of specific mixing power input based on total solids in the sludge (W/kgTS) is proposed to achieve maximum biogas production using optimum power input. The relationship has its limitations, but it represents a significant step forward in the design and operation of improved digester mixing systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, laboratory scale digesters were operated to simulate potential shocks to the Anaerobic Digestion (AD) process at a 350 ML/day wastewater treatment plant. The shocks included high (42 °C) and low (32 °C) temperature (either side of mesophilic 37 °C) and a 20% loading of fats, oil and grease (FOG; 20% w:v). These variables were explored at two sludge retention times (12 and 20 days) and two organic loading rates (2.0 and 2.5 kgTS/m(3)day OLR). Metagenomic and metabolomic approaches were then used to characterise the impact of operational shocks in regard to temperature and FOG addition, as determined through monitoring of biogas production, the microbial profile and their metabolism. Results showed that AD performance was not greatly affected by temperature shocks, with the biggest impact being a reduction in biogas production at 42 °C that persisted for 32 ± 1 days. The average biogas production across all digesters at the completion of the experiment was 264.1 ± 76.5 mL/day, with FOG addition observed to significantly promote biogas production (+87.8 mL/day). Metagenomic and metabolomic analyses of the digesters indicated that methanogens and methane oxidising bacteria (MOB) were low in relative abundance, and that the ratio of oxidising bacteria (methane, sulphide and sulphate) with respect to sulphate reducing bacteria (SRB) had a noticeable influence on biogas production. Furthermore, increased biogas production correlated with an increase in short chain fatty acids, a product of the addition of 20% FOG. This work demonstrates the application of metagenomics and metabolomics to characterise the microbiota and their metabolism in AD digesters, providing insight to the resilience of crucial microbial populations when exposed to operational shocks., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this article, I share some thoughts about how we might extend the study of mental health inequalities by drawing from key insights in sociology and sociological social psychology about the nature of inequality and the processes through which it is produced, maintained, and resisted. I suggest several questions from sociological research on stratification that could help us understand unexpected patterns of mental health inequalities. I also advocate for the analysis of "generic" social psychological processes through which inequalities are produced, maintained, and resisted within proximate social environments. I consider the role of two such processes--status/devaluation processes and identity processes--in mental health inequalities. I then discuss how we can strengthen connections across subfields of the sociology of mental health by applying status and identity theories to two areas of research: (1) help-seeking and (2) the effects of mental health problems on social attainments., (© American Sociological Association 2015.)

Anaerobic digestion of sewage sludge is highly complex and prone to inhibition, which can cause major issues for digester operators. The result is that there have been numerous investigations into changes in operational conditions, however to date all have focused on the qualitative sensitivities, neglecting the quantitative. This study therefore aimed to determine the quantitative sensitivities by using factorial design of experiments and small semi continuous reactors. Analysis showed total and volatile solids removals are chiefly influenced by retention time, with 79% and 59% of the observed results being attributed to retention time respectively, whereas biogas was mainly influenced by loading rate, 38%, and temperature, 22%. Notably the regression model fitted to the experimental data predicted full-scale performance with a high level of precision, indicating that small reactors are subject to the same sensitivity of full-scale digesters and thus can be used to predict changes loading, retention time, and temperature., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Enhanced prospects for natural gas production raise questions about the balance of impacts on air quality, as increased emissions from production activities are considered alongside the reductions expected when natural gas is burned in place of other fossil fuels. This study explores how trends in natural gas production over the coming decades might affect emissions of greenhouse gases (GHG), volatile organic compounds (VOCs) and nitrogen oxides (NOx) for the United States and its Rocky Mountain region. The MARKAL (MARKet ALlocation) energy system optimization model is used with the U.S. Environmental Protection Agency's nine-region database to compare scenarios for natural gas supply and demand, constraints on the electricity generation mix, and GHG emissions fees. Through 2050, total energy system GHG emissions show little response to natural gas supply assumptions, due to offsetting changes across sectors. Policy-driven constraints or emissions fees are needed to achieve net reductions. In most scenarios, wind is a less expensive source of new electricity supplies in the Rocky Mountain region than natural gas. U.S. NOx emissions decline in all the scenarios considered. Increased VOC emissions from natural gas production offset part of the anticipated reductions from the transportation sector, especially in the Rocky Mountain region.

Introduction: Juvenile fibromyalgia syndrome (JFS) is a medically unexplained illness that can cause persistent, diffuse pain in a child or adolescent. This pain can lead to anxiety or depression and absence from school or work, and it can adversely affect a child's quality of life and family relationships. Prompt recognition of JFS may decrease problems for pediatric patients with chronic pain, but pediatric primary care providers' lack of familiarity with JFS can cause a delay in diagnosis., Method: A project using a developed screening tool, the SORE Scoresheet, was implemented in the pediatric clinic at Kaiser Permanente Fontana from September 2011 to January 2012. Pediatric providers were educated about the tool before the project began., Results: Twenty-two patients with JFS were referred with use of the SORE Scoresheet. Symptoms of JFS matched at a rate of 93% between the providers and the rheumatologist, and a reduction in the number of weeks to referral and the number of visits before referral was found compared with a sample of patients with JFS from 2010., Conclusion: Pediatric provider education and development of a screening tool assists with the recognition of JFS., (Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.)

This review will discuss policies that influenced medical home establishment and involvement of nurse practitioners, the background of the pediatric medical home, challenges, successful programs, and recommendations.

Adrenomedullin (AM) is a novel vasodilatatory peptide which acts primarily through the calcitonin receptor-like receptor (CLR) in combination with either receptor-activity-modifying-protein (RAMP) 2 or 3 (forming receptors, AM(1) and AM(2) respectively). AM plays an important role during inflammation, with its expression increasing following cytokine treatment, promoting macrophage action in situ and high expression by T cells during hypoxic conditions. Examination of T cell AM receptor expression has previously been incomplete, hence we here consider the presentation of AM receptors and their responsiveness to AM and glucocorticoids (GC). AM receptor expression was examined by PCR and flow cytometry in primary human T cells, revealing that RAMP2, 3 and CLR are physiologically expressed in unstimulated T cells, both intracellularly and on the cell surface. PHA stimulation decreased receptor proteins, significantly so for CLR and RAMP3. Incubation with AM elicited limited receptor alterations however, GC treatment (10(-6) M; 24 h) markedly affected cell surface expression, significantly increasing receptor components in unstimulated cells and significantly decreasing the same in stimulated T cells. Our findings indicate that human T cells utilize both AM(1) and AM(2) receptors, which are GC-sensitive in an activation-state dependent manner., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study examined the associations of substance use, psychological distress, and mental health services receipt with the structure and content of adolescent school-based networks. Using data from the National Longitudinal Study of Adolescent Health, we found that substance use was associated with receiving more, but making fewer, peer nominations. It also was associated with less favorable network characteristics, such as low GPA. Services receipt was associated with receiving and making fewer nominations, less favorable network characteristics, and a lower likelihood of reciprocated best friendships. Psychological distress had fewer significant associations. All associations were modest in magnitude. Our results suggest the importance of considering multiple indicators of socioemotional problems and multiple dimensions of social networks in research on adolescent peer relations.

Prior research on the association of mental health and behavior problems with academic achievement is limited because it does not consider multiple problems simultaneously, take co-occurring problems into account, and control for academic aptitude. We addressed these limitations using data from the National Longitudinal Study of Adolescent Health (N = 6,315). We estimated the associations of depression, attention problems, delinquency, and substance use with two indicators of academic achievement (high school GPA and highest degree received) with controls for academic aptitude. Attention problems, delinquency, and substance use were significantly associated with diminished achievement, but depression was not. Combinations of problems involving substance use were especially consequential. Our results demonstrate that the social consequences of mental health problems are not the inevitable result of diminished functional ability but, rather, reflect negative social responses. These results also encourage a broader perspective on mental health by demonstrating that behavior problems heighten the negative consequences of more traditional forms of distress.

The aim of this study was to investigate the transferability of technology and reproducibility of MUTZ-3 derived Langerhans Cell (MUTZ-LC) migration assay. The protocol was transferred from the NL-lab to two Sens-it-iv project partners (UK-lab, Italy-lab). Intra- and inter-laboratory variation with regards to MUTZ-3 progenitor culture, differentiation to MUTZ-LC, maturation and migration assay were investigated. In the transwell-migration-assay, preferential migration of sensitizer-exposed MUTZ-LC towards CXCL12 was observed (three sensitizers), whereas non-sensitizer-exposed MUTZ-LC only migrated towards CCL5 (two non-sensitizers). Four pre-pro-haptens were also identified by UK-lab. When taking the arbitrary criteria of at least two of three independent repetitions per laboratory having to have a CXCL12/CCL5 ratio>1.1 for classification as a sensitizer, all sensitizers tested in all labs were easily distinguished from all non-sensitizers. The number of repetitions giving false negative or false positive was very low (only 7 out of a total of 54 repetitions), indicating that both intra- and inter-laboratory variation was extremely low. Even though only a few chemicals were tested in this study, we show clearly that the in vitro DC migration assay is transferable between laboratories. The results were consistent between the laboratories, and the dose response data were reproduced in the three laboratories., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The development of novel in vitro methods to assess risks of allergic sensitization are essential in reducing animal testing whilst maintaining consumer safety. The main research objectives of this study were to identify novel biomarkers to assess the sensitization predictability of chemicals. Phenotypic and cytokine responses of moDCs and MUTZ-3 cells were investigated following application of contact sensitizers; dinitrochlorobenzene (DNCB), cinnamaldehyde (Cin), eugenol (E), isoeugenol (IE), P-phenylenediamine (PPD) and non-sensitizers; salicyclic acid (SA) and sodium lauryl sulphate (SLS). CD86 was up-regulated on MUTZ-3 cells in response to DNCB, Cin and PPD, however, moDCs only modulated CD86 in response to DNCB and E. PDL-1 (Programmed death receptor ligand-1) proved a promising sensitization biomarker in MUTZ-3 cells where up-regulation occurred in response to DNCB, Cin, IE and PPD. Additionally, moDC-expressed PDL-1 was modulated in response to Cin, IE and E thus demonstrating improved sensitizer predictability when compared with CD86. MCP-1 and RANTES were identified as biomarkers of DNCB exposure but MCP-1 did not show any change in expression above controls for the other sensitizers investigated. However, RANTES was increased in MUTZ-3 cells by both DNCB and Cin. Our findings highlight novel biomarkers which, in MUTZ-3 cells, could be taken forward within a multiple biomarker in vitro assay ensuring strong and reliable predictability., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Context: Research on the association between socioemotional problems and early sexual initiation has not evaluated differences across types of problems, by gender, or by race or ethnicity., Methods: Data were analyzed for a sample derived from the Children of the National Longitudinal Surveys of Youth: 1,836 youth who were 10-11 years old at the 1992, 1994 and 1996 waves. Mothers' reports of their child's socioemotional problems at age 10-11 were assessed; sexual initiation before age 15 was assessed using youth self-reports. Logistic regression analyses estimated associations between socioemotional problems and early initiation; predicted probabilities and group differences were calculated using various regression techniques., Results: Twenty-six percent of youth had had intercourse before turning 15, and their average level of each problem was higher than the level of those who had not. Both internalizing problems (e.g., depression and dependency) and externalizing problems (e.g., hyperactivity and antisocial behavior) were associated with early sexual initiation (odds ratios, 1.1 and 1.2, respectively), but only externalizing problems retained significance when both types were included in the model (1.2). Among specific problems, only hyperactivity and antisocial behavior were associated with early initiation (1.2 for each). Youth with a high level of externalizing problems had a higher predicted probability of having early sex than did those with a low level (0.28 vs. 0.21). Associations between socioemotional problems and early initiation did not differ by gender or by race or ethnicity., Conclusions: Interventions should be targeted at youth with externalizing problems, especially those who engage in antisocial or hyperactive behavior, in an effort to promote positive social interactions.

There is an accumulating evidence for the immunoregulatory role of the neuropeptide, nociceptin/orphanin FQ (N/OFQ) however its role on T cell function requires elucidation. This study has demonstrated an inhibitory role for N/OFQ on SEB-activated T cell function. N/OFQ decreases T cell proliferation, which is abrogated when the costimulatory receptors CD80 and CD86 are blocked. In addition, evidence suggests that the immunoregulatory cytokines TGF-beta, IFN-gamma and nitric oxide (NO) are involved in the N/OFQ effect. N/OFQ also, through involvement of IFN and NO, induces the expression of the immunosuppressive modulator indoleamine 2,3-dioxygenase (IDO), suggesting a central role for IDO in the N/OFQ effect on T cell proliferation. The data presented in this report indicate a multi-faceted mechanism of action used by N/OFQ to modulate T cell function.

Dendritic cells (DC) are sensitive to their local environment and are affected by proximal cell death. This study investigated the modulatory effect of cell death on DC function. Monocyte-derived DC exposed to apoptotic Jurkat or primary T cells failed to induce phenotypic maturation of the DC and were unable to support CD4+ allogeneic T-cell proliferation compared with DC exposed to lipopolysaccharide (LPS) or necrotic cells. Apoptotic cells coincubated with LPS- or necrotic cell-induced mature DC significantly suppressed CD80, CD86 and CD83 and attenuated LPS-induced CD4+ T-cell proliferation. Reduced levels of interleukin-12 (IL-12), IL-10, IL-6, tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) were found to be concomitant with the suppressive activity of apoptotic cells upon DC. Furthermore, intracellular staining confirmed IFN-gamma expression by DC in association with apoptotic environments. The specific generation of IFN-gamma by DC within apoptotic environments is suggestive of an anti-inflammatory role by the induction of indoleamine 2,3-dioxygenase (IDO). Both neutralization of IFN-gamma and IDO blockade demonstrated a role for IFN-gamma and IDO in the suppression of CD4+ T cells. Moreover, we demonstrate that IDO expression within the DC was found to be IFN-gamma-dependent. Blocking transforming growth factor-beta (TGF-beta) also produced a partial release in T-cell proliferation. Our study strongly suggests that apoptosis-induced DC suppression is not an immunological null event and two prime mediators underpinning these functional effects are IFN-gamma-induced IDO and TGF-beta.

The authors draw on developmental psychopathology, life course sociology, and scholarship on educational processes to develop a conceptual framework for understanding the association of children's mental health problems with educational attainment. They use this framework to address two empirical gaps in prior research: lack of attention to mental health trajectories and the failure to consider diverse explanations. Using data from the Children of the National Longitudinal Surveys of Youth data set, the authors identify latent classes that characterize trajectories of internalizing and externalizing problems from childhood through adolescence. Youths in the classes vary significantly in their likelihoods of high school completion and college entry. The authors evaluate the ability of three sets of mediators to explain these patterns: academic aptitude, disruptive behaviors, and educational expectations. Educational expectations are important mediators independent of academic aptitude and disruptive behaviors. Social responses to youths' mental health problems contribute importantly to their disrupted educational trajectories.

Squamous metaplasia in the tracheobronchial epithelium (TBE) involves the replacement of the normal pseudostratified mucociliary epithelium with a stratified squamous epithelium. Squamous metaplasia is considered to be an adaptive response that protects the lumen from the effects of inhaled airborne pollutants, but which might also feature as a pre-neoplastic lesion preceding squamous cell carcinoma. With the exception of transglutaminase I, involucrin, and cytokeratins 5, 6 and 13, few markers that contribute to the squamous phenotype have been identified in human TBE that can be used in diagnosis or to monitor its development in laboratory investigations, and current models are inadequate to provide statistically meaningful data. Therefore, new predictive markers have been identified, and new techniques established, in epithelial in vitro models capable of expressing squamous characteristics, which will be used to identify hazardous exposures and elucidate the mechanisms by which they induce their effects. A protocol for the quantitative detection of transglutaminase activity has been standardised in keratinocytes, based on the enzymatic incorporation of fluorescein-cadaverine (FC) into bis(gamma-glutamyl) polyamine cross-links. The specificity of this compound as a transglutaminase substrate was demonstrated by using a range of competitive transglutaminase inhibitors, and by modulation of the squamous pathway. FC incorporation was localised to the cell membrane of terminally differentiating cells, and was not visible in basal, proliferating cells. High calcium-containing medium, nicotine and cigarette smoke condensates (CSC) induced an increase in FC incorporation, providing evidence of their role in enhancing the squamous pathway. Analysis by flow cytometry was used to provide a quantitative assessment of a range of optimised squamous differentiation markers, identified in normal human bronchial epithelia and in a bronchial cell line. Transglutaminase I was induced in a time-dependent manner, in post-confluent cells induced to differentiate down the squamous pathway, whereas involucrin was ubiquitously expressed and the levels of cytokeratins 5, 6 and 18 were reduced. The response of these and other differentiation markers to squamous-inducing conditions is being explored.

Objectives: Data on community responses to two treatment issues critical for children and adolescents with mental health problems are addressed: stigma associated with receiving mental health care and the willingness to use psychiatric medication., Methods: Using a representative sample of the U.S. population, the investigators interviewed 1,393 noninstitutionalized adult participants in the National Stigma Study-Children (NSS-C) (response rate 70%; margin of error +/- 4%)., Results: Many respondents believed that stigma results from mental health treatment during childhood (45% reported likely rejection at school) and that stigma continues to have negative ramifications into adulthood (43%). More than half (57%) were skeptical about confidentiality, and more than one-third (35%) expected parents of children with mental illness to experience self-stigma. Most respondents believed that psychiatric medications affect development (68%), give children a flat, "zombie"-like affect (53%), and delay solving "real" behavior-related problems (66%). Most (86%) believed that physicians overmedicate children for common behavioral problems. Women and persons with more education rather than less perceived less stigma resulting from treatment but reported more negative views on medication. Beliefs in medication efficacy and trust in physicians were associated with more positive cultural beliefs., Conclusions: Data on the contemporary cultural context surrounding treatment for children's mental health issues revealed substantial stigma concerns, particularly surrounding medication options. These beliefs and attitudes cannot be easily inferred from adults' sociodemographic characteristics.

Objective: This study examined the public's beliefs regarding the potential for harm to self and others and the public's willingness to invoke coercive or legal means to ensure treatment of children., Methods: Using data from the National Stigma Study-Children (NSS-C), which presented vignettes to 1,152 individuals, the investigators compared public perceptions of the dangerousness of children with attention-deficit hyperactivity disorder (ADHD), major depression, asthma, and "daily troubles." Multivariate analyses were used to examine the predictors of perceptions of dangerousness and the willingness to support legally enforced treatment of these conditions., Results: Children with ADHD and children with major depression were perceived (by 33% and 81% of the sample, respectively) as somewhat likely or very likely to be dangerous to themselves or others, compared with children with asthma (15%) or those with "daily troubles" (13%). Over one-third of the sample (35%) were willing to use legal means to force children with depression to see a clinician. However, even more (42%) endorsed forced treatment for a child with asthma. Furthermore, individuals who labeled the child as "mentally ill" were approximately twice as likely to report a potential for violence and five times as likely to support forced treatment., Conclusions: Large numbers of people in the United States link children's mental health problems, particularly depression, to a potential for violence and support legally mandated treatment. These evaluations appear to reflect the stigma associated with mental illness and the public's concern for parental responsibility.

Debates about children's mental health problems have raised questions about the reliability and validity of diagnosis and treatment. However, little research has focused on social reactions to children with mental health problems. This gap in research raises questions about competing theories of stigma, as well as specific factors shaping prejudice and discrimination toward those children. Here, we organize a general model of stigma that synthesizes previous research. We apply a reduced version of this model to data from a nationally representative sample responding to vignettes depicting several stigmatizing scenarios, including attention-deficit/hyperactivity disorder (ADHD), depression, asthma, or "normal troubles." Results from the National Stigma Study-Children suggest a gradient of rejection from highest to lowest, as follows: ADHD, depression, "normal troubles," and physical illness. Stigmatizing reactions are highest toward adolescents. Importantly, respondents who label the vignette child's situation as a mental illness compared to those who label the problem as a physical illness or a "normal" situation report greater preferences for social distance, a pattern that appears to result from perceptions that the child is dangerous.

Interest in income inequality as a predictor of health has exploded since the mid-1990s. Recent analyses suggest, however, that the effect of income inequality on population health is not robust to a control for the racial composition of the population. That observation raises two interpretational questions. First, does income inequality have an independent effect on population health? Second, what does the effect of racial composition on population health mean? We use data from the Urban Institute's Assessing the New Federalism project and the Kids Count Databook to evaluate the aggregate effects of income inequality on diverse measures of child well-being (e.g., infant mortality, high school drop-out rates) in the 50 U.S. states. We replicate the finding that, net of the racial/ethnic composition of the population, the effects of income inequality are not significant. Moreover, the effects of racial composition on child well-being appear to be compositional (i.e., they reflect the less positive outcomes observed among racial/ethnic minorities) rather than contextual (i.e., representing the independent influence of social context). Whereas cross-level effects are still possible, our results cast doubt on the health relevance of these aggregate characteristics of the population.

T-cell clones (TCC) derived from human peripheral blood lymphocytes of a young control, a healthy elderly (SENIEUR) donor, or from CD34(+) hematopoietic progenitor cells were utilised in this study to examine how in vivo and in vitro ageing affects T-cell apoptotic capability. The role of CD25, CD28 and the intracellular proteins, FLICE-inhibitory protein (FLIP), receptor-interacting protein (RIP) and caspase 3 were investigated. We observed an age-related decline in the expression of the IL-2 receptor alpha chain CD25, and absence of the co-stimulatory receptor CD28 on three of the four TCC studied. In young donor- and CD34 cell-derived TCC, but not in SENIEUR donor-derived TCC, we observed an age-related increase in susceptibility of the cells to mFas-L-induced apoptosis, which correlated with the age-related decrease of CD25 expression. Expression levels of full-length RIP and FLIP did not show any correlation to apoptotic susceptibility. However, expression levels of the cleaved form of RIP were greatly reduced in the SENIEUR donor-derived TCC, which together with a trend towards increased caspase 3 activity, could indicate an age-related alteration in utilisation of different apoptotic signalling pathways.

Although nociceptin/orphanin FQ (N/OFQ) and its receptor (ORL-1) are widely distributed throughout the immune system, its role has yet to be elucidated. This study shows that N/OFQ (10(-14)-10(-12) M) modulates T cell activation by up-regulating activation marker expression, e.g. CD28, leading to enhanced proliferation and modulation of TNFalpha secretion. However, on re-stimulated T cells N/OFQ causes inhibition of proliferation, which could be linked with N/OFQ up-regulating CTLA-4 expression. We have also shown that some of these effects are partly prostaglandin-dependent and that N/OFQ induces prostaglandin synthesis. This report suggests that N/OFQ could exert a key modulatory role in human T cell functions.

Psychiatric medication use for children has increased dramatically over the past three decades. Despite substantial media attention to the issue, little is known about how the lay public feels about the use of psychiatric medications for children. Drawing on theories of medicalization, we describe and analyze Americans' attitudes towards the use of psychiatric medications generally and Prozac specifically for children described as having three types of behavioral problems. Using data from the 1998 General Social Survey's Pressing Issues in Health and Medical Care Module, we find that more Americans (57%) are willing to use psychiatric medications for children who have expressed suicidal statements than for "oppositional" behaviors (34.2%) or for hyperactivity (29.5%). Across the board, respondents are less willing to give Prozac than the general class of psychiatric medications. While socio-demographics do little to identify Americans with differing positions, the strongest and most consistent correlates of willingness to give psychiatric medications to children are trust in personal physicians, general attitudes towards psychiatric medications, and the respondent's expressed willingness to take psychiatric medications herself or himself.

The previously determined crystal structure of the superantigen staphylococcal enterotoxin C2 (SEC2) showed binding of a single zinc ion located between the N- and C-terminal domains. Here we present the crystal structure of SEC2 determined to 2.0 A resolution in the presence of additional zinc. The structure revealed the presence of a secondary zinc-binding site close to the major histocompatibility complex (MHC)-binding site of the toxin and some 28 A away from the primary zinc-binding site of the toxin found in previous studies. T cell stimulation assays showed that varying the concentration of zinc ions present affected the activity of the toxin and we observed that high zinc concentrations considerably inhibited T cell responses. This indicates that SEC2 may have multiple modes of interaction with the immune system that are dependent on serum zinc levels. The potential role of the secondary zinc-binding site and that of the primary one in the formation of the TCR.SEC2.MHC complex are considered, and the possibility that zinc may regulate the activity of SEC2 as a toxin facilitating different T cell responses is discussed.

CD95-induced apoptosis is an important regulatory mechanism in T cells and this complex signalling pathway is now thought to include the protein kinase RIP. Although, RIP is best known for its role in TNF signalling and NF-kappaB activation, it contains a death domain and it is capable of causing apoptosis upon cleavage. In the present study, the role of RIP in CD95-induced apoptosis and its inter-relationship with the caspase cascade was investigated. Studies were performed on both a RIP-/- T cell line and peripheral T lymphocytes, where RIP was degraded through the addition of geldanamycin. Apoptosis was induced by membrane CD95-L, thought to be the most physiological relevant form of CD95-L. Results showed that RIP-/- cells had a decreased susceptibility to death, thus confirming a role for RIP in CD95-induced apoptosis. Furthermore, it was confirmed that RIP is cleaved upon CD95-L stimulation, a process that can be inhibited by Z-VAD. However, only partial inhibition in peripheral T lymphocytes by Z-VAD was observed, suggesting a potential caspase-independent processing of RIP. Studies performed on the activity of effector caspase 3 and on the initiator caspases 2, 8, and 9 revealed that, in the absence of RIP, the activity of these caspases decreases, indicating that RIP-associated apoptosis is caspase-dependent. Hence, these studies support a caspase-related role for RIP in CD95-induced T apoptosis.

P-glycoprotein (Pgp) is a membrane transporter responsible for resistance to chemotherapy in cancer cells. Its presence in T cells is very well documented, but its function in the immune system is still poorly understood. Recent findings suggest that Pgp may be involved in regulating programmed cell death by inhibiting caspase 8 and caspase 3. Utilising antigenically-activated T cells and the physiologically relevant apoptotic ligand, membrane CD95-L, we have previously reported that while T cells are generally resistant to CD95-induced death at early stages of activation, their susceptibility to apoptosis increases with successive activation and clonal expansion. In this study we investigated whether changes in apoptotic susceptibility were related to T cell Pgp function. Results showed that Pgp expression and function in T cells decreases with maturation, with CD8 cells having the highest Pgp function. However, although Pgp function inversely correlated with caspase 3 activity, no difference was observed between apoptotic susceptible CD25- cells and resistant CD25+ cells. In addition sorting of cells with high and low Pgp function showed no correlation with apoptotic capability. Therefore, whilst Pgp modulates caspase activity, it is not responsible for resistance to apoptosis of early activated T cells nor the increased susceptibility observed at the later stages of maturation in antigenically activated cells.

Neuro-inflammation is characterized by immune cell infiltration across the blood-brain barrier, a process instrumental in neuronal cell death. In neuro-inflammation the blood-brain barrier is also damaged and the consequences of activated lymphocytes on the integrity of the blood-brain barrier is not well characterized. Utilizing an blood-brain barrier model we demonstrate that endothelial cell viability and barrier integrity are directly altered following lymphocyte exposure. The effect of activated lymphocytes is cell number dependent, mostly mediated by direct contact, and is not associated with the pro-inflammatory cytokine TNF-alpha. For the successful treatment of neuro-inflammatory disease, intervention of this direct effect at the blood-brain barrier is warranted.

In this study we evaluated the role of the multi-drug transporter p-glycoprotein (Pgp) in the process of activated T lymphocyte-mediated blood-brain barrier dysfunction as described previously. Lymphocyte exposure induced significant endothelial cell death and there was an elevation of the expression of Pgp in the surviving cells. Inhibition of Pgp function using the antibody MRK16 and verapamil displayed a dose-dependent prevention of T cell mediated endothelial cell death and barrier breakdown. These data suggest that the activity of Pgp at the blood-brain barrier may play a role in lymphocyte induced barrier cell damage and a role as a possible survival mechanism to prevent further endothelial cell death in later stages of inflammation.

Immunosenescence is believed to contribute to increase susceptibility to infectious diseases and cancer in the elderly, and is caused mainly by changes in the T cell compartment. Longitudinal studies were undertaken to examine T cell surface receptor expression and apoptotic susceptibility using Staphylococcal enterotoxin B (SEB) activated human T cells as an in vitro model of an ageing T cell culture. An intracellular stain Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to assess the number of population divisions (PD) occurring in the ageing T cell culture. One major biomarker of aged T cells is a decrease in expression of CD28 and since this is an essential co-stimulatory molecule, its decreasing expression with age could compromise their activation and apoptotic capacity. Activation of T cells resulted in initial up-regulation of CD25, CD95 and CD28, although expression of CD25 and CD28 subsequently decreased with increasing PD. CD4 and CD8 T cells expressed similar CD25 profiles although CD28 expression was unique in each subset. CD4+ cells expressed the highest CD28 levels, and showed a gradual decline in expression with increasing PD, whereas CD8+ cells were low CD28 expressers, but did not appear to lose their expression as they aged. To determine T cell susceptibility to apoptosis via CD95/CD95-L interactions with increasing age, cells were challenged with CD95-L transfected CHO cells at various PD. Increased death was observed as they aged, which correlated with the decreased expression of activation markers CD25 and CD28.

The ageing immune system shows a gradual decline in responsiveness to antigens and tumours due to the emergence of immunosenescence. The main functions of T cells are activation, anergy and apoptosis and these are all affected during ageing. Apoptosis is vital in controlling cell numbers, deleting self-reactive T cells and maintaining immune surveillance. One of the principle instigators of death involves the CD95:CD95-ligand interaction and as T cells age both receptor and ligand levels increase. This view will describe the current knowledge of the apoptotic susceptibility of ageing T cells and evaluate the factors that may affect the apoptotic capability of immunosenescent T cells.

The generation of effective immunity requires that antigen-specific T cells are activated, clonally expanded and ultimately eliminated by apoptosis. The involvement of CD95-mediated apoptosis in T-cell elimination is well established, but the conditions which regulate the death pathway under normal circumstances are still emerging. Using superantigen-activated human T cells, we found that whilst T-cell receptor (TCR) signalling triggered up-regulation of CD95 ligand (CD95L), the majority of T cells were resistant to apoptosis induction, despite co-expressing high levels of CD95. Resistance was maintained following direct antibody-mediated cross-linking of CD95 and was not confined to early time periods following activation. Our data implicate TCR-derived signals in protection from apoptosis and reveal a role for the mitogen-activated protein (MAP) kinase pathway by use of a MAP kinase kinase (MEK) inhibitor. Collectively these data demonstrate that resistance to activation-induced cell death in human T cells is prolonged rather than transient, is not attributable to a lack of CD95L up-regulation and is due, at least in part, to signalling via the MEK pathway.

Although the role of CD28 in T cell costimulation is firmly established, the mechanisms by which it exerts its costimulatory actions are less clear. In many circumstances it is difficult to distinguish the effects of CD28 from subsequent actions of cytokines, such as IL-2, on T cell proliferation. Here, we report a model of CD28 costimulation using PMA plus the natural ligand CD80 that resulted in very limited stimulation of IL-2, as evidenced by both cytokine production and IL-2 promoter stimulation. Promoter assays revealed CD28-dependent effects on both NF-kappaB and AP-1, but not on NF-AT or the intact IL-2 promoter. In addition, T cell proliferation was completely resistant to the actions of the immunosuppressant cyclosporin A (CsA). Moreover T cell proliferation was unaffected by the addition of blocking Abs to both IL-2 and the IL-2 receptor, demonstrating that this form of costimulation by CD28 was independent of IL-2. We also investigated the effects of stimulating T cell blasts with CD80 alone and found that there was a limited requirement for IL-2 in this system. We conclude that CD28 costimulation can cause substantial T cell proliferation in the absence of IL-2, which is driven by a soluble factor independent of NF-AT transactivation.

CD28 and CTLA-4 are related receptors that differentially regulate T cell activation. Despite the fact that they bind the same ligands, CD28 is a classical costimulator enhancing proliferation whereas CTLA-4 appears to perform negative regulatory functions. In this study, we have utilized the natural ligand for CD28 and CTLA-4 (CD80) to determine under what circumstances positive and negative effects are operative. We show here that the stimulation of purified human T cells with phorbol ester and ionomycin is inhibited in the presence of Chinese hamster ovary (CHO) cells expressing CD80. This inhibition is reversed by blocking with both anti-CD80 or Fab fragments of anti-CTLA-4 but also requires CD28 engagement. Furthermore, we show that the inhibitory function of CD80 requires elevated intracellular calcium since inhibition was observed only in the presence of ionomycin. In the absence of intracellular calcium elevation, CTLA-4 was not expressed at the cell surface, and CD80 acted positively as a costimulator of T cells, via CD28. These results demonstrate that the natural ligand CD80 can either costimulate or inhibit T cell responses depending on the conditions of T cell stimulation.

Following antigen engagement of the T-cell receptor (TCR), T-cell survival is largely dictated by the provision of additional signals, such as those from costimulatory receptors and cytokine receptors. Whilst CD28-mediated signalling is increasingly associated with survival, ligation of alternative T-cell antigens, such as Fas (CD95), can trigger apoptosis. The T-cell response following antigen engagement may therefore be influenced by the relative expression levels of these coreceptors as well as by the availability of their ligands (CD80/86 and Fas-L). In this study we demonstrate functional interplay between the death receptor Fas and the costimulatory receptor CD28 in human T cells. In Jurkat T cells, we show that Fas signalling leads to rapid and selective CD28 down-regulation, and that this is associated with a specific decrease in mRNA for CD28, indicating that mechanisms exist which target CD28 at a transcriptional level. Moreover, cells that down-regulate CD28 also undergo apoptosis. Studies on activated human peripheral blood T cells demonstrate that cells expressing high levels of CD28 are resistant to Fas-mediated apoptosis whereas cells expressing low levels are more susceptible, implicating CD28 in the provision of anti-apoptotic signals. Consistent with this hypothesis, direct ligation of CD28 using B7 transfectants concomitant with anti-Fas challenge protects from apoptosis. Since antigen-presenting cells may express Fas-L under certain circumstances, the maintenance of T-cell CD28 expression may be crucial for the prevention of Fas-mediated apoptosis during the course of antigen engagement.

Ag recognition is an essential component for an effective T cell response. However, T cell activation is also subject to additional regulation by accessory molecules. CD28 provides essential costimulatory signals that allow T cells to proliferate, whereas molecules such as CTLA-4 and CD95 (Fas) appear to be negative regulators. Currently, which outcome predominates under conditions of antigenic challenge is poorly understood. In particular it has been suggested that one consequence of antigenic activation of T cells is the up-regulation of both CD95 and CD95 ligand, thereby exposing activated T cells to apoptotic death. We have investigated this possibility in normal human peripheral blood T cells triggered by the superantigen SEB either in the presence of endogenous APCs or transfectants expressing DR4 and CD80. In either case, we find that such activation does not expose the majority of T cells to anti-CD95-induced apoptosis as detected by annexin V externalization and DNA fragmentation. Furthermore, by phenotypically identifying, by flow cytometry, those cells that received both antigenic and costimulatory signals from those cells that did not, we observed that CD95-induced apoptosis was not seen in activated T cells receiving Ag and costimulatory signals via CD28. However, while not all T cells were stimulated by superantigen, CD95 expression was found to be homogeneously up-regulated, suggesting a mechanism whereby bystander cells might be made susceptible to CD95-induced death. We conclude that antigenic activation of T cells via the TCR and CD28 engagement provides protection from CD95-induced apoptosis.

Using data from three waves of the Children of the National Longitudinal Surveys of Youth data set (1986, 1988, 1990), we examine the dynamic relationship between children's family histories of poverty and their developmental trajectories of mental health. Children who were poor in 1986 or who had prior histories of poverty had higher levels of depression and antisocial behavior in that year. Furthermore, subsequent poverty histories were also related to children's mental health trajectories. The number of years that children were poor between 1986 and 1990 correlates significantly with changes in children's antisocial behavior during those years. Finally, rates of increase in antisocial behavior were substantially higher for children with histories of persistent poverty during those years than for transiently poor or nonpoor children. These results demonstrate the accelerating behavioral disadvantages faced by persistently poor children.

Glucocorticoid-induced changes in cellular levels of Lipocortin-1 (LC-1) (Annexin 1) in C6 glioma cells were determined by electrotransfer and immunoblotting techniques. Separate cell protein fractions were prepared to study the influence of the glucocorticoid steroid, dexamethasone, on LC-1 localisation. Cells were grown in steroid-depleted medium and exposed to dexamethasone (10(-8) and 10(-7) M) for 2, 6, and 16 hr. The glucocorticoid-dependent changes in cellular content of LC-1 were both dose- and time-related. Increases above control levels in intracellular and extracellular LC-1 content were detected with the greatest changes occurring at the cell surface. The glucocorticoid-dependent alteration in LC-1 distribution in C6 glioma cells was attenuated by the protein synthesis inhibitor, cycloheximide, indicating the involvement of de novo LC-1 synthesis. The significance of these results is discussed in relation to the current concept that some of the anti-inflammatory effect of glucocorticoids occurs through the action of extracellular LC-1.

1. The antiinflammatory actions of glucocorticoid steroids are thought to occur through induction of the protein lipocortin-1 (LC-1; annexin-1). The purpose of the current study was to investigate whether astrocytic LC-1 content was increased in the presence of a synthetic glucocorticoid, dexamethasone. 2. Steroid-induced changes in cellular levels of LC-1 in astrocytes were determined by electrotransfer and immunoblotting techniques. Separate cell fractions were investigated to study the influence of dexamethasone on astroglial LC-1 content. The effect of culture state on LC-1 expression was also examined. 3. Intracellular LC-1 content was found to decrease after initiation of culture, with a substantial rise in both cell proliferation and LC-1 expression occurring after the replenishment of medium containing steroid-free serum. A further increase in intracellular LC-1 occurred upon incubation with dexamethasone. The glucocorticoid-induced change in intracellular LC-1 was a time-dependent event and coincided with an increase in membrane-associated LC-1. 4. The findings in this study indicate that astrocytic LC-1 content is influenced by cell culture conditions and, in the presence of glucocorticoid steroids, the cellular localization of LC-1 is altered. This may indicate that LC-1 has functions at more than one cellular locality.

This study compared perceived marital quality among couples in which neither, one, or both spouses met criteria for an anxiety disorder. Phobic husbands and their wives reported poorer marital quality than did other spouses. Husbands' panic disorders had similar but weaker effects on perceived marital quality, and wives' panic disorders predicted poor perceived marital quality by by husbands. Wives with generalized anxiety disorder perceived their marriages to be less satisfying than did other wives. The effects of husbands' generalized anxiety disorders were strongest in the presence of comorbid depression or alcohol or drug dependence but the effects of husbands' phobias and of panic disorders did not vary with comorbidity. Spouse concordance for phobias was related to more favorable marital reports, but concordance for other anxiety disorders was unrelated to marital quality.

Using data from a community sample of 586 married couples, levels of spouse concordance for lifetime and current alcohol dependence and heavy drinking were estimated. In addition, marital quality ratings in concordant and discordant couples were compared. Spouse concordance was significant for lifetime alcohol dependence and for both lifetime and current heavy drinking. Marital quality varied as a function of current heavy drinking and alcohol dependence such that members of couples in which neither spouse drank heavily reported better marital quality than other couples. Furthermore, although marital quality did not differ significantly between concordant and discordant couples, couples concordant for current heavy drinking consistently reported poorer marital quality than other couples.