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The number of youth presenting to Emergency Departments (EDs) with psychiatric chief complaints has almost doubled in the last decade. With pediatric patients, ED brief interventions and discharge recommendations necessitate meaningful parental engagement to optimize youth safety and support. This study examined parent-level factors (stigmatizing attitudes, self-efficacy beliefs, distress symptoms, and illness-related stressors) in relation to parents' behavioral engagement (i.e., participation in and follow-through with best practice discharge recommendations). In this short-term prospective study, participants were 118 parent-youth (aged 11-18) dyads (57% female) recruited from a psychiatric ED. Parents' behavioral engagement was measured with parent- and youth-self report at 2-week follow-up. Parents' self-reported anxious and depressive symptoms, insomnia, stress, and stigmatizing attitudes were not related to engagement 2 weeks later. Higher parental self-efficacy beliefs were significantly associated with greater engagement in standard discharge recommendations. Implications for maximizing parent implementation of clinical recommendations during a youth suicide crisis are discussed.

Objective: Given increases in mental health utilization among college and university students, this study examines clinical and socio-demographic characteristics in students presenting to psychiatr...

Depression and suicidal ideation have substantially increased among college students, yet many students with clinically significant symptoms do not perceive their distress as warranting mental health services. Personalized feedback (PF) interventions deliver objective data, often electronically, comparing an individual’s reported symptoms or behaviors to a group norm. Several studies have shown promise for PF interventions in the context of mood and depression, yet little is known regarding how, and for whom, mood-focused PF interventions might be best deployed. The primary aim of this study was to examine the sociodemographic, clinical, and treatment-seeking factors associated with reviewing PF reports on emotional distress among college students (N=1,673) screening positive for elevated suicide risk and not receiving mental health treatment. Results indicated that PF engagement was greatest among those with higher depression scores, and those reporting privacy/stigma concerns as barriers to treatment. Sexual minority students were more likely to review their PF than heterosexual students. Taken together, PF interventions may be a useful tool for engaging those with greater clinical acuity, and those hesitant to seek in-person care. Further research is warranted to examine the circumstances in which PF interventions might be used in isolation, or as part of a multi-tiered intervention strategy.

The streaming series 13 Reasons Why generated controversy because of its depiction of teen suicide and concerns about its impact on vulnerable youths. This study examined exposure to and patterns of engagement with the show and the show's perceived impact in a sample of youths presenting to a psychiatric emergency department (ED) with suicide-related concerns in the year after the series' premiere.Participants were 87 parent-youth dyads (youths' mean±SD age=14.6±1.8; 71% of youths were female, 26% male, and 2% gender nonconforming) who completed a battery of questionnaires during their ED visit.Half (49%) of the sample viewed at least one episode of 13 Reasons Why, season 1. Most youths (84%) viewed the show alone and were more likely to discuss their reactions with peers (80%) than with a parent (34%). Over half of youth viewers (51%) believed the series increased their suicide risk to a nonzero degree; having a stronger identification with the lead female character was significantly related to this belief (r=.63, df=41, p0.001). Youths with more depressive symptoms and suicidal ideation were more likely to identify with the lead characters and report negative affect while viewing.To date, this is the first published study examining viewing patterns and reactions to 13 Reasons Why in a high-risk sample. Although further research is needed, the findings suggest a particular vulnerability to the show's themes among youths at risk of suicide and the importance of prevention strategies to ameliorate risk among these viewers.

Patients with borderline personality disorder (BPD) are high utilizers of psychiatric emergency services and present unique challenges in that setting. Frequently advised to visit an emergency department (ED) if safety is in question, their experiences once there often do not have beneficial effects. Issues specific to patients with BPD in the ED include volatile interactions with staff, repeat visits, concerns about safety (and liability), and disposition. Emergency department staff attitudes toward these patients are frequently negative when compared to patients with other diagnoses, and can detrimentally affect outcomes and perpetuate stigma regarding BPD. These attitudes are often due to lack of education and training about how to understand, approach, and treat the patient with BPD. The limited literature regarding the treatment of BPD in the ED offers few guidelines. This article presents an approach based on Good Psychiatric Management that can reduce negative reactions by ED staff and make ED visits more effective and less harmful. Relevant principles include psychoeducation, the reinforcement of the connection between symptoms and interpersonal stressors, and employment of an active, authentic therapeutic stance. Training ED staff in these principles could lead to attitudinal changes, reduced stigma, and potentially improved outcomes.

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90α binding assay (IC(50) = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC(50) = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qd × 5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

RORγt is a pivotal regulator of a pro-inflammatory gene expression program implicated in the pathology of several major human immune-mediated diseases. Evidence from mouse models demonstrates that genetic or pharmacological inhibition of RORγ activity can block the production of pathogenic cytokines, including IL-17, and convey therapeutic benefit. We have identified and developed a biaryl-carboxylamide series of RORγ inverse agonists via a structure based design approach. Co-crystal structures of compounds 16 and 48 supported the design approach and confirmed the key interactions with RORγ protein; the hydrogen bonding with His479 was key to the significant improvement in inverse agonist effect. The results have shown this is a class of potent and selective RORγ inverse agonists, with demonstrated oral bioavailability in rodents.

Interest has arisen in recent years in the relationship between religious involvement and health outcomes. Although most of the early literature consists of studies with methodological flaws, some recent well-conducted reports show that religious attendance is associated with reduced mortality in selected subgroups and populations.In this study, we investigated the relationship between religious attendance and mortality using the 14,456 participants in the National Institute of Aging-funded 'Established Populations for Epidemiologic Studies of the Elderly'.Our analyses show that after controlling for important prognostic factors, frequent religious attendance was associated with increased survival in the entire cohort [risk ratio (RR) = 0.78, 95% Confidence interval (CI) 0.70-0.88]. However, stratified analyses show that this association exists for only two of the four sites.We conclude that the association between religious attendance and survival is not robust and may depend upon unknown confounders and covariates.

To evaluate the effects of HSP90 blockade by EC154 on the oncogenic receptor tyrosine kinase macrophage-stimulating 1 receptor (MST1R) in gastric and pancreatic cancer.Impact of EC154 on signaling pathways was investigated by western blotting. Cancer cell migration was evaluated in Boyden chambers. Transcriptional regulation of MST1R was examined by using promoter-luciferase reporter constructs. Effects on MST1R expression, and tumor growth were investigated in in vivo tumor models.MST1R was expressed by cancer cells without evidence of MST1R mutations. EC154 led to an effective inhibition of cancer cell growth, down-regulated MST1R, diminished its promoter activity, and disrupted oncogenic macrophage-stimulating protein 1 (MSP1) signaling. Moreover, pro-migratory activities of cancer cells were dramatically inhibited. In vivo, treatment with EC154 significantly reduced tumor growth, while MST1R expression was down-regulated.Wild-type MST1R is an HSP90 client protein that can be targeted in gastrointestinal cancer using HSP90 inhibitors.

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, plays a crucial role in B-cell maturation and mast cell activation. Although the structures of the unphosphorylated mouse BTK kinase domain and the unphosphorylated and phosphorylated kinase domains of human ITK are known, understanding the kinase selectivity profiles of BTK inhibitors has been hampered by the lack of availability of a high resolution, ligand-bound BTK structure. Here, we report the crystal structures of the human BTK kinase domain bound to either Dasatinib (BMS-354825) at 1.9 Å resolution or to 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 Å resolution. This data provides information relevant to the development of small molecule inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases. Analysis of the structural differences between the TEC and Src families of kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain suggests a mechanism of regulation of the TEC family members.