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Abstract. Background: Suicide risk following youth psychiatric hospitalization is of significant concern. This study evaluated Linking Individuals Needing Care (LINC), a theory-driven, comprehensive care coordination approach for youth discharged from crisis services. Aims: To pilot LINC's potential effectiveness in increasing service utilization and decreasing suicide risk. Method: Participants were 460 youth patients who received LINC for approximately 90 days following discharge from crisis services. Service utilization, depressive symptoms, and suicide-related variables were measured at baseline and 30, 60, and 90 days after baseline. Results: Patients significantly increased the use of various beneficial, least restrictive services (individual therapy, medication management, and non-mental health supports) over the 90-day intervention. Significant decreases were observed in depressive symptoms, suicide ideation, and engagement in suicide-related behaviors. Limitations: Absence of a comparison group and nonparticipating families limit causal conclusions and generalizability. Conclusions: LINC may be a promising new approach following inpatient hospitalization that can engage and retain youth in services, likely resulting in improved treatment outcomes. This approach was designed emphasizing patient engagement, suicide risk assessment and management, safety planning, community networking, referral/linkage monitoring, coping and motivational strategies, and linguistic/culturally responsive practices to meet service and support needs of high-risk suicidal youth.

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

Individuals who identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ) are at a higher risk for suicidality compared to the general population. A growing body of research has investigated this risk, particularly with attention to systemic factors such as discrimination and harassment. Unfortunately, research has only examined the impact of direct discrimination on suicidality and has neglected to examine how ambient discrimination (i.e., witnessing or being made aware of discriminatory behaviors directed at someone other than yourself in your group) relates to suicidality. Additionally, although some links exist between discrimination and suicidality, the mechanisms by which these are related are understudied. This study aimed to address these gaps by exploring the effect of ambient discrimination on suicidal ideation and examining psychological pain as a mediator in this relationship. Data were collected from a sample of 200 LGBTQ-identified individuals (M age = 35 years; 53.5% female; 86% White). Results of independent t tests and a one-way multivariate ANOVA revealed greater vulnerability for ambient/direct discrimination and psychache among individuals identifying as transgender, queer, and other. Regression and mediation analyses revealed that while both ambient and direct discrimination predicted suicidal ideation, only direct discrimination accounted for unique variance in the outcome; however, both ambient and direct discrimination contributed unique variance to psychological pain, which fully mediated their relationships to suicidal ideation. Results of this study may begin to provide insight into the pathways of risk and points of intervention for suicidality in the LGBTQ community.

Although emotion regulation has been identified as a key function of non-suicidal self-injury (NSSI), it is unclear how specific indices of emotion regulation are associated with particular NSSI methods as markers of risk. This study used latent class analysis (LCA) to identify subgroups of individuals who engage in NSSI and their patterns of emotional regulation difficulties. Undergraduate students in the southeastern United States (N = 326) completed an online survey. LCA was used to identify subgroups of individuals engaging in NSSI and their associated emotion regulation difficulties. These subgroups were then compared across a variety of behavioral health outcomes (e.g. impulsive behavior, disordered eating, problematic alcohol use, suicide attempt history) to characterize specific risk profiles. The LCA revealed four subgroups who engage in NSSI and have specific emotion regulation difficulties. These subgroups were differentially associated with behavioral health outcomes, including suicide risk, disordered eating, and impulsive behavior. Results of this research could aid in clinical identification of at-risk individuals.

Most eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3’ untranslated region in order to regulate mRNA function. Here, we present a systematic analysis of 3’ end formation factors, which revealed 3’UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3’UTRs. We show that the anti-cancer drug cordycepin, 3’ deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin-mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of an rpb1 mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3’ end processing and controlled by the availability of 3’ end factors, nucleotide levels and chromatin landscape.

Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes in macrophages have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of βAR signalling on macrophage metabolism has not been defined. Using metabolomics and proteomics, we describe the impact of βAR signalling on macrophages treated with isoprenaline. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox homeostasis of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate and guanylate pools. Taken together, these results indicate that βAR signalling shifts metabolism to support redox processes and upregulates proteins involved in cytoskeletal changes, which may contribute to βAR effects on macrophage function.

Suicide rates continue to rise, and clinicians and mental health staff play a critical role in keeping suicidal clients safe. Safety planning, including means safety, may help to decrease suicide risk. Unfortunately, availability and evaluation of safety planning training for these providers are scarce. The goal of the present study was to evaluate a safety planning training, LINC to LIFE Safety Planning (L2L SP). L2L SP is a 150-minute, face-to-face training program that teaches providers to engage clients in collaborative safety planning and means safety efforts, facilitate diverse client coping strategies, problem-solve, and involve close others, among other skills. These objectives are achieved through interactive content delivery, role-play, and corrective feedback. L2L SP was administered to 95 participants. Key determinants of behavioral change (e.g., knowledge, attitudes, perceived behavioral control [PBC]) were measured at pre, post, and six-month follow-up. Additionally, participants' behaviors and emotions in working with suicidal clients were measured at pretest and six-month follow-up. Paired sample t-tests, repeated measures MANOVA, and univariate ANOVAs with post-hoc testing using Bonferroni correction were conducted. Results supported significant improvements in knowledge, PBC, and intentions at post-test, and attitudes, PBC, and effective emotional responses at follow-up. Exploratory analyses suggested significant improvements in behaviors among clinicians and mental health staff who saw clients reporting suicidal ideation. The present study provides promising results regarding brief safety planning training. Declines in knowledge and PBC following the training highlight the potential need for booster sessions or more intensive initial training in these areas.HighlightsThe present study evaluated a comprehensive, interactive safety planning training.Knowledge, PBC, and intentions were significantly improved at post-test.Attitudes, PBC, and emotions were significantly improved at follow-up.

Most eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3’ untranslated region in order to regulate mRNA function. Here we present a systematic analysis of 3’ end formation factors, which revealed 3’UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3’UTRs. We show that the anti-cancer drug cordycepin, 3’ deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of anrpb1mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3’ end processing and controlled by the availability of 3’ end factors, nucleotide levels and chromatin landscape.

Veteran and service member suicide remains a significant public health concern. One factor that may impact suicide risk is suicide exposure—knowing someone who has died by suicide or attempted suicide. However, the majority of the extant literature has focused on nonmilitary samples, which may not generalize to military veterans and service members. The current review synthesizes findings regarding suicide exposure in military veterans, service members, their families, and military systems. Our review suggests that the relationship between suicide exposure, suicide risk, and mental health outcomes remains inconsistent. Future research should further explore this important area.

Individuals who identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ) are at a higher risk for suicidality compared to the general population. A growing body of research has investigated this risk, particularly with attention to systemic factors such as discrimination and harassment. Unfortunately, research has only examined the impact of direct discrimination on suicidality and has neglected to examine how ambient discrimination (i.e., witnessing or being made aware of discriminatory behaviors directed at someone other than yourself in your group) relates to suicidality. Additionally, although some links exist between discrimination and suicidality, the mechanisms by which these are related are understudied. This study aimed to address these gaps by exploring the effect of ambient discrimination on suicidal ideation and examining psychological pain as a mediator in this relationship. Data were collected from a sample of 200 LGBTQ-identified individuals (M age = 35 years; 53.5% female; 86% White). Results of independent t tests and a one-way multivariate ANOVA revealed greater vulnerability for ambient/direct discrimination and psychache among individuals identifying as transgender, queer, and other. Regression and mediation analyses revealed that while both ambient and direct discrimination predicted suicidal ideation, only direct discrimination accounted for unique variance in the outcome; however, both ambient and direct discrimination contributed unique variance to psychological pain, which fully mediated their relationships to suicidal ideation. Results of this study may begin to provide insight into the pathways of risk and points of intervention for suicidality in the LGBTQ community.

// Heidi A. Neubauer 1,2 , Duyen H. Pham 1,2 , Julia R. Zebol 1 , Paul A.B. Moretti 1 , Amanda L. Peterson 4 , Tamara M. Leclercq 1 , Huasheng Chan 1,2 , Jason A. Powell 1,3 , Melissa R. Pitman 1 , Michael S. Samuel 1,3 , Claudine S. Bonder 1,2,3 , Darren J. Creek 4 , Briony L. Gliddon 1 and Stuart M. Pitson 1,2,3 1 Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia 2 School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia 3 School of Medicine, University of Adelaide, Adelaide, South Australia, Australia 4 Monash Institute of Pharmaceutical Science, Monash University, Parkville, Victoria, Australia Correspondence to: Stuart M. Pitson , email: // Keywords : sphingosine kinase 2, neoplastic transformation, oncogenesis, proliferation, tumorigenesis Received : June 08, 2016 Accepted : August 25, 2016 Published : August 30, 2016 Abstract While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an anti-proliferative/pro-apoptotic function for SK2, while others indicate it has a pro-survival role and its inhibition can have anti-cancer effects. Our analysis of gene expression data revealed that SK2 is upregulated in many human cancers, but only to a small extent (up to 2.5-fold over normal tissue). Based on these findings, we examined the effect of different levels of cellular SK2 and showed that high-level overexpression reduced cell proliferation and survival, and increased cellular ceramide levels. In contrast, however, low-level SK2 overexpression promoted cell survival and proliferation, and induced neoplastic transformation in vivo . These findings coincided with decreased nuclear localization and increased plasma membrane localization of SK2, as well as increases in extracellular S1P formation. Hence, we have shown for the first time that SK2 can have a direct role in promoting oncogenesis, supporting the use of SK2-specific inhibitors as anti-cancer agents.