Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2

Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for β-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif–like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G–opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor κB by β-glucan–containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor α. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms

Combatting dependency and promoting child protection in Rwanda

Continuing dependence on aid that waxes and wanes with time and that comes largely from external sources can lead to feelings of powerlessness. It can furthermore undermine family- and community-based initiatives to protect children

Risk Factors for Non-Initiation of the Human Papillomavirus (HPV) Vaccine among Adolescent Survivors of Childhood Cancer

Effective vaccination is now available to prevent human papillomavirus (HPV), the most common sexually transmitted infection and cause of cervical cancer. This study aimed to estimate the prevalence of HPV vaccination among childhood cancer survivors and identify factors associated with HPV vaccine initiation and completion. Mothers of daughters aged 9–17 years with/without a history of childhood cancer (n = 235, Mage= 13.2 years, SD= 2.69; n = 70, Mage= 13.3 years, SD=2.47, respectively) completed surveys querying HPV vaccination initiation and completion along with socio-demographic, medical, HPV knowledge and communication, and health belief factors, which may relate to vaccination outcomes. Multivariate logistic regression was utilized to identify factors which associate with HPV vaccination initiation and completion. Among cancer survivors, 32.6% initiated and 17.9% completed the 3-dose vaccine series, whereas 34.3% and 20.0% of controls initiated and completed, respectively. Univariate analyses indicated no differences between cancer/no cancer groups on considered risk factors. Among all participants, multivariate logistic regression analyses found vaccine initiation associated with older age of daughter and physician recommendation, while increased perceived barriers associated with a decreased likelihood of initiation (all Ps \u3c .05). Among those having initiated, risk factors for non-completion included being non-white, increased perceived severity of HPV, and increased perceived barriers to vaccination (all Ps \u3c .05). A minority of adolescents surviving childhood cancer have completed vaccination despite their increased risk for HPV-related complication. These results inform the prioritization of strategies to be included in vaccine promotion efforts

Parent Management Training and Collaborative & Proactive Solutions: A Randomized Control Trial for Oppositional Youth

This study examined the efficacy of Collaborative & Proactive Solutions (CPS) in treating oppositional defiant disorder (ODD) in youth by comparing this novel treatment to Parent Management Training (PMT), a well-established treatment, and a waitlist control (WLC) group. One hundred thirty-four youth (ages 7-14, 61.9% male, 83.6% White) who fulfilled Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for ODD were randomized to CPS, PMT, or WLC groups. ODD was assessed with semistructured diagnostic interviews, clinical global severity and improvement ratings, and parent report measures. Assessments were completed pretreatment, posttreatment, and at 6 months following treatment. Responder and remitter analyses were undertaken using intent-to-treat mixed-models analyses. Chronological age, gender, and socioeconomic status as well as the presence of comorbid attention deficit/hyperactivity and anxiety disorders were examined as predictors of treatment outcome. Both treatment conditions were superior to the WLC condition but did not differ from one another in either our responder or remitter analyses. Approximately 50% of youth in both active treatments were diagnosis free and were judged to be much or very much improved at posttreatment, compared to 0% in the waitlist condition. Younger age and presence of an anxiety disorder predicted better treatment outcomes for both PMT and CPS. Treatment gains were maintained at 6-month follow-up. CPS proved to be equivalent to PMT and can be considered an evidence-based, alternative treatment for youth with ODD and their families

Parent Management Training and Collaborative & Proactive Solutions: A Randomized Control Trial for Oppositional Youth.

This study examined the efficacy of Collaborative & Proactive Solutions (CPS) in treating oppositional defiant disorder (ODD) in youth by comparing this novel treatment to Parent Management Training (PMT), a well-established treatment, and a waitlist control (WLC) group. One hundred thirty-four youth (ages 7-14, 61.9% male, 83.6% White) who fulfilled Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for ODD were randomized to CPS, PMT, or WLC groups. ODD was assessed with semistructured diagnostic interviews, clinical global severity and improvement ratings, and parent report measures. Assessments were completed pretreatment, posttreatment, and at 6 months following treatment. Responder and remitter analyses were undertaken using intent-to-treat mixed-models analyses. Chronological age, gender, and socioeconomic status as well as the presence of comorbid attention deficit/hyperactivity and anxiety disorders were examined as predictors of treatment outcome. Both treatment conditions were superior to the WLC condition but did not differ from one another in either our responder or remitter analyses. Approximately 50% of youth in both active treatments were diagnosis free and were judged to be much or very much improved at posttreatment, compared to 0% in the waitlist condition. Younger age and presence of an anxiety disorder predicted better treatment outcomes for both PMT and CPS. Treatment gains were maintained at 6-month follow-up. CPS proved to be equivalent to PMT and can be considered an evidence-based, alternative treatment for youth with ODD and their families

Identifying the best parameters to determine genotype capability to retain adequate malic acid at harvest and in final wines

Maintaining optimal grape acidity at harvest is one of the most complicated challenges under climate change pressures, especially in early ripening cultivars. Warming trends are compressing vine phenology and fostering berry malic acid respiration. In this work, over four years, we evaluated yield components and fruit ripening in two local varieties in the Colli Piacentini, Ortrugo (ORT) and Barbesino (BRB). Our goal was to evaluate their ability to maintain satisfying acidity at harvest and understand the limits and features of the genetic control over organic acid degradation during ripening. The two varieties exhibited comparable yield and grape total soluble solids (TSS) accumulation dynamics, but BRB showed consistently higher acidity during the entire ripening process in any of the four years. BRB's higher acidity was linked to higher malic acid concentrations. ORT had earlier onset of malic acid degradation than BRB and lower maximum malic acid degradation rates. Malic acid degradation rates were lower in ORT also later in the season, until harvest. However, correlations built between malic acid degradation rates and instantaneous malic acid concentration revealed that BRB had a consistently lower malic acid loss for values of malate &lt; 10 g/L. Our work demonstrates that there is a genetic control over the malic acid degradation rates exhibited at varying malic acid concentrations and higher acidity at harvest can be found in varieties exhibiting low malic acid degradation rates when malic acid is &lt; 10 g/L. Post-veraison berry growth rates could interact with genotype effects. The analysis of the correlation can be used at different scales to identify cultivars retaining higher acidity at harvest