Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.

Worsening Symptoms of Anxiety, Depression, and Sleep Problems in Caregivers Following Youth's Suicide-Related Emergency Department Visit.

OBJECTIVE: Although families assume considerable responsibility in caring for their child after a suicidal crisis, little is known about caregiver well-being following a suicide-related pediatric Emergency Department (ED) visit. This study aimed to (1) describe the course of caregiver distress symptoms (e.g., anxiety, depression, and negative affect) and sleep problems following their child's suicide-related ED visit and to (2) identify factors (e.g., parents' mental health history, youth suicide risk chronicity, and perception of feeling supported by the mental health system) hypothesized to be related to caregiver distress symptoms and sleep problems at follow-up using a diathesis-stress model framework. METHOD: Participants included 118 caregiver/youth (ages 11-17) dyads presenting to a psychiatric ED due to youths' suicide-related concerns. Caregivers and youth were assessed during index ED visit and 2-weeks following discharge. RESULTS: Caregivers' anxiety and depressive symptoms and sleep problems increased significantly from the time of the ED visit to 2-week follow-up. There was no significant change in caregiver negative affect. Caregivers with their own history of mental illness and those whose children had a previous ED visit due to a psychiatric concern, suggestive of chronic suicide risk, reported higher anxiety and depressive symptoms at follow-up. CONCLUSION: In the 2 weeks following an ED visit for their child's suicidal crisis, caregivers reported significant increases in anxiety and depressive symptoms and sleep problems. Findings highlight the need to consider the mental health of caregivers whose children are at elevated risk for suicide.HighlightsCaregivers report increases in distress symptoms following youth's suicidal crisis.Caregiver mental health history and youth suicide chronicity impacted distress.Caregiver mental health should be considered when planning youth interventions.

Delphi consensus study to develop guidelines for the management of adults with borderline personality disorder in the emergency department: a protocol.

INTRODUCTION: Clinicians caring for adults with borderline personality disorder (BPD) in acute settings such as the emergency department (ED) have little evidence/guidance to base decisions on. Specific/detailed guidance for managing BPD in the ED is needed given the morbidity and mortality risks, high service utilisation, unique challenges and risk of iatrogenic interventions. The primary objective of this study is to use a consensus method to develop a guideline for managing adults with BPD in the ED. This protocol and the key questions for the guideline were developed with the advice of people with BPD and their family members/support persons. METHODS AND ANALYSIS: We will perform a four-phase Delphi study of an expert panel of clinicians, researchers, adults with BPD and their family members/support persons. Various disciplines (psychiatry, psychology, emergency medicine, nursing, social work) and treatment approaches will be included in the expert panel. An online questionnaire will be developed from systematic reviews, qualitative assessments of pivotal literature, and opinions suggested by the panel (phase 1). The panel will rate their agreement on opinions for each key question covering areas of emergency care of adults with BPD using two rounds of this questionnaire (phases 2 and 3). Opinions meeting predefined thresholds for consensus will be brought to consensus meetings moderated by an independent chair (phase 4). The purpose of these meetings is to finalise the set and phrasing of the opinions for each area of emergency care. These final opinions will be the recommendations in the guideline. If there are significant differences of opinion, the guideline will present both recommendations alongside one another. ETHICS AND DISSEMINATION: This study has received ethics approval by the Hamilton Integrated Research Ethics Board in Hamilton, Ontario, Canada. The results of this study will be disseminated through peer-reviewed publications, conferences and national professional and patient/family/support associations.

Ecological Momentary Assessments and Passive Sensing in the Prediction of Short-Term Suicidal Ideation in Young Adults.

Importance: Advancements in technology, including mobile-based ecological momentary assessments (EMAs) and passive sensing, have immense potential to identify short-term suicide risk. However, the extent to which EMA and passive data, particularly in combination, have utility in detecting short-term risk in everyday life remains poorly understood. Objective: To examine whether and what combinations of self-reported EMA and sensor-based assessments identify next-day suicidal ideation. Design, Setting, and Participants: In this intensive longitudinal prognostic study, participants completed EMAs 4 times daily and wore a sensor wristband (Fitbit Charge 3) for 8 weeks. Multilevel machine learning methods, including penalized generalized estimating equations and classification and regression trees (CARTs) with repeated 5-fold cross-validation, were used to optimize prediction of next-day suicidal ideation based on time-varying features from EMAs (affective, cognitive, behavioral risk factors) and sensor data (sleep, activity, heart rate). Young adult patients who visited an emergency department with recent suicidal ideation and/or suicide attempt were recruited. Identified via electronic health record screening, eligible individuals were contacted remotely to complete enrollment procedures. Participants (aged 18 to 25 years) completed 14 708 EMA observations (64.4% adherence) and wore a sensor wristband approximately half the time (55.6% adherence). Data were collected between June 2020 and July 2021. Statistical analysis was performed from January to March 2023. Main Outcomes and Measures: The outcome was presence of next-day suicidal ideation. Results: Among 102 enrolled participants, 83 (81.4%) were female; 6 (5.9%) were Asian, 5 (4.9%) were Black or African American, 9 (8.8%) were more than 1 race, and 76 (74.5%) were White; mean (SD) age was 20.9 (2.1) years. The best-performing model incorporated features from EMAs and showed good predictive accuracy (mean [SE] cross-validated area under the receiver operating characteristic curve [AUC], 0.84 [0.02]), whereas the model that incorporated features from sensor data alone showed poor prediction (mean [SE] cross-validated AUC, 0.56 [0.02]). Sensor-based features did not improve prediction when combined with EMAs. Suicidal ideation-related features were the strongest predictors of next-day ideation. When suicidal ideation features were excluded, an alternative EMA model had acceptable predictive accuracy (mean [SE] cross-validated AUC, 0.76 [0.02]). Both EMA models included features at different timescales reflecting within-day, end-of-day, and time-varying cumulative effects. Conclusions and Relevance: In this prognostic study, self-reported risk factors showed utility in identifying near-term suicidal thoughts. Best-performing models required self-reported information, derived from EMAs, whereas sensor-based data had negligible predictive accuracy. These results may have implications for developing decision algorithms identifying near-term suicidal thoughts to guide risk monitoring and intervention delivery in everyday life.

KMU-191 Induces Apoptosis in Human Clear Cell Renal Cell Carcinoma Caki Cells Through Modulation of Bcl-xL, Mcl-1 (L), c-FLIP (L), and p53 Proteins.

The anti-proliferative effects of a newly developed N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191, have been previously evaluated in various cancer cells. However, the detailed anti-cancer molecular mechanisms of KMU-191 remain unknown. In this study, we investigated anti-cancer mechanisms by which KMU-191 regulates apoptosis-related genes in human clear cell renal cell carcinoma Caki cells. KMU-191 induced poly ADP-ribose polymerase cleavage and caspase-dependent apoptosis. In addition, KMU-191 induced down-regulation of the long form of cellular FADD-like IL-1ß-converting enzyme inhibitory protein (c-FLIP (L)) at the transcriptional level as well as that of long form of myeloid cell leukemia (Mcl-1 (L)) and B-cell lymphoma-extra large at the post-transcriptional level. Furthermore, KMU-191-induced apoptosis was closely associated with the Mcl-1 (L) down-regulation, but also partially associated with c-FLIP (L) down-regulation. In contrast, KMU-191 up-regulated p53, which is closely related to KMU-191-induced apoptosis. Although KMU-191 showed cytotoxicity of normal cells, it unusually did not induce cardiotoxicity. Taken together, these results suggest that a multi-target small molecule, N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191 is a potential anti-cancer agent that does not induce cardiotoxicity.

Acceptability and feasibility of ecological momentary assessment with augmentation of passive sensor data in young adults at high risk for suicide.

Ecological Momentary Assessment (EMA) and wearable sensor data have the potential to enhance prediction of suicide risk in real-world conditions. However, the feasibility of this methodology with high-risk populations, including over extended periods, warrants closer attention. This study examined the feasibility and acceptability of concurrent EMA and wearable sensor monitoring in young adults after emergency department (ED) care for suicide risk-related concerns. For 2 months after ED discharge, 106 participants (ages 18-25; 81.1% female) took part in EMA surveys (4x per day) and passive sensor (Fitbit) monitoring and completed an end-of-study phone interview. Overall adherence to EMA (62.1%) and wearable sensor (53.6%) was moderate and comparable to briefer protocols. Relative to EMAs (81%), fewer participants completed the full 8 weeks of Fitbit (63%). While lower initial hopelessness was linked to reduced EMA adherence, previous-day suicidal ideation predicted lower Fitbit adherence on the next day. Self-endorsed barriers to EMA and wearable sensor adherence were also examined. Participants tended to report positive experience with the protocol, with majority indicating EMAs were minimally burdensome, reporting that the Fitbit was generally comfortable, and expressing interest in participating in a similar study again. Findings provide support for the feasibility and acceptability of concurrent intensive self-report and wearable sensor data during a high-risk period. Implications and future directions are discussed.

Updates in the Assessment and Management of Agitation.

Agitated patients can be dangerous to themselves and others. In fact, severe medical complications and death can occur with severe agitation. Because of this, agitation is considered a medical and psychiatric emergency. Regardless of the treatment setting, identifying the agitated patient early is a necessary skill. The authors review relevant literature regarding the identification and management of agitation and summarize current recommendations for adults, as well as children and adolescents.

Predictors of suicide coping self-efficacy among youth presenting to a psychiatric emergency department.

INTRODUCTION: Low levels of youth-reported self-efficacy to cope with suicidal urges have been shown to prospectively predict repeat emergency department (ED) visits and suicide attempts, yet little is known about how self-efficacy may change following receipt of crisis services or about factors that may strengthen self-efficacy. Protective factors (e.g., parent-reported youth competence, parent-family connectedness, and receipt of mental health services) were examined in relation to self-efficacy at the time of a psychiatric ED visit and 2 weeks later. METHODS: Participants were 205 youth (ages 10-17), presenting to a psychiatric ED due to a suicide-related concern. Youth primarily identified as biological female (63%) and White (87%). Multivariate hierarchical linear regressions were used to examine candidate protective factors in relation to initial and follow-up suicide coping self-efficacy. RESULTS: Self-efficacy significantly improved in the 2 weeks following the ED visit. Parent-family connectedness was positively related to suicide coping self-efficacy at the time of the ED visit. Parent-family connectedness and receipt of inpatient psychiatric care following the ED visit were associated with higher follow-up suicide coping self-efficacy. CONCLUSIONS: During the adolescent developmental period when suicidal thoughts and behaviors notably increase, study findings highlight potential malleable intervention targets, including parent-family connectedness, that may strengthen suicide coping self-efficacy.

A 6-year retrospective review of psychiatric emergency service utilization by school-age children.

To explore utilization patterns and associated clinical factors of school-age children who present to a psychiatric emergency department. This was a 6-year retrospective chart review study of children 5-12 years of age who presented to a psychiatric emergency service from July 2012 to June 2018 (n = 1654 patients). Demographic variables, clinical diagnoses, lifetime adverse events (physical abuse, sexual abuse, and bullying), and history of self-harm were documented for each visit. We performed a chi square analysis to identify association between demographic and clinical features with key outcomes. Increased service utilization as defined by inpatient psychiatric admission, recurrent visits, or increased length of stay were found in patients who were adopted, presented with suicidal ideation or self-harm behaviors, had a history of abuse, and had a diagnosis of depression or autism. Trends over the course of the study indicated a significantly increased percentage of patients presenting with suicidal ideation, bullying, and self-harm behaviors. The data add to the limited literature regarding school-age children with a psychiatric emergency. Increased emergency service utilization for certain subgroups of children and trends over the course of the study underscore the need for enhanced treatment options for individuals with certain demographic or clinical features, and increased outpatient, intermediate, and inpatient treatment options, as well as preventative care.

Impact of the COVID-19 Pandemic on Children and Adolescents Presenting With a Psychiatric Emergency.

This mixed-methods survey study aims to describe the effects of the COVID-19 pandemic on the mental health of a sample of 571 children and adolescent seeking psychiatric emergency care. The study was conducted from July to October 2020 at a large Midwestern academic center. Among the respondents, there were significant increases in mental health symptoms attributed to the COVID-19 pandemic, including anxiety (71% of respondents), depression (66%), suicidal thoughts or behaviors (45%), and aggression (31%). There were significant differences in reported increases in symptoms by age and gender. In addition, 38% of participants reported that the pandemic led to a change or closure of their health care treatment, including mental health providers, with 22% reporting that reduced treatment access led to their emergency visit. Further research is indicated to assess other, more diverse populations, as well as the longer-term mental health impacts of the pandemic.

Engagement With Personalized Feedback for Emotional Distress Among College Students at Elevated Suicide Risk.

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 multitiered intervention strategy.

Predictors of Parent Behavioral Engagement in Youth Suicide Discharge Recommendations: Implications for Family-Centered Crisis Interventions.

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.

University students presenting for psychiatric emergency services: Socio-demographic and clinical factors related to service utilization and suicide risk.

ObjectiveGiven increases in mental health utilization among college and university students, this study examines clinical and socio-demographic characteristics in students presenting to psychiatric emergency services. Participants: University students (N = 725; Mage = 22 years, SD = 4.0; 67% White) visiting psychiatric emergency services at a large academic health system between July 1, 2012 and June 30, 2016. Methods: A retrospective review of students' electronic medical records, which included responses to the Columbia-Suicide Severity Rating Scale, was conducted. Results: Levels of suicide risk varied by students' self-identified race. Nonwhite students were more likely to endorse a suicide attempt in the past week and less likely to be taking psychiatric medications than White students. International students were more likely to report a lifetime history of multiple attempts. Conclusions: Disparities related to college student psychiatric emergencies warrant specific attention to specific racial/ethnic groups and international students to reduce and manage mental health crises.

2-Thioxothiazolidin-4-one Analogs as Pan-PIM Kinase Inhibitors.

Proviral integration site for Moloney murine leukemia virus (PIM) kinases are proto-oncogenic kinases involved in the regulation of several cellular processes. PIM kinases are promising targets for new drug development because they play a major role in many cancer-specific pathways, such as survival, apoptosis, proliferation, cell cycle regulation, and migration. Here, 2-thioxothiazolidin-4-one derivatives were synthesized and evaluated as potent pan-PIM kinase inhibitors. Optimized compounds showed single-digit nanomolar IC50 values against all three PIM kinases with high selectivity over 14 other kinases. Compound 17 inhibited the growth of Molm-16 cell lines (EC50 = 14 nM) and modulated the expression of pBAD and p4EBP1 in a dose-dependent manner.

Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.

Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.

Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization-Based Assay.

The serum- and glucocorticoid-regulated kinase (SGK) family consists of three isoforms (SGK1, SGK2, and SGK3) that have been implicated in the regulation of tumor growth, metastasis, autophagy, and epithelial ion transport. SGK1 and SGK3 play essential roles in protein kinase B (AKT or PKB)-independent phosphoinositide 3-kinases (PI3K)-mediated tumorigenesis, as evidenced by the significantly elevated expression levels of SGK1 and SGK3 in many cancers, including prostate cancer, colorectal carcinoma, estrogen-dependent breast cancer, and glioblastoma. Therefore, SGK is a potential target for anticancer therapy. A small kinase-focused library comprising 160 compounds was screened against SGK1 using a fluorescence polarization-based kinase assay that yielded a Z'-factor of 0.82. Among the 39 compounds obtained as initial hits in a primary screen, 12 compounds contained the thiazolidine-2,4-dione scaffold. The inhibitory mechanisms of the most potent hit, KMU010402, were further investigated using kinetic analyses, followed by determination of the inhibition constants for SGK1, SGK2, and SGK3. Molecular modeling was used to propose a potential binding mode of KMU010402 to SGK1.

KMU-1170, a Novel Multi-Protein Kinase Inhibitor, Suppresses Inflammatory Signal Transduction in THP-1 Cells and Human Osteoarthritic Fibroblast-Like Synoviocytes by Suppressing Activation of NF-κB and NLRP3 Inflammasome Signaling Pathway.

Protein kinases regulate protein phosphorylation, which are involved in fundamental cellular processes such as inflammatory response. In this study, we discovered a novel multi-protein kinase inhibitor, KMU-1170, a derivative of indolin-2-one, and investigated the mechanisms of its inflammation-inhibiting signaling in both THP-1 cells and human osteoarthritic fibroblast-like synoviocytes (FLS). We demonstrated that in THP-1 cells, KMU-1170 inhibited lipopolysaccharide (LPS)-induced upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and, furthermore, suppressed LPS-induced phosphorylation of transforming growth factor-ß-activated kinase 1, JNK, ERK, inhibitor of NF-κB kinase α/ß (IKKα/ß), and NF-κB p65 as well as nuclear translocation of NF-κB p65. Moreover, KMU-1170 suppressed LPS-induced upregulation of proinflammatory cytokines such as IL-1ß, TNF-α, and IL-6, and, notably, inhibited LPS-induced upregulation of the NLRP3 inflammasome in THP-1 cells. Importantly, KMU-1170 attenuated LPS-mediated inflammatory responses in human osteoarthritic FLS, such as the upregulation of IL-1ß, TNF-α, IL-6, iNOS, and COX-2 and the phosphorylation of IKKα/ß and NF-κB p65. Collectively, these results suggest that KMU-1170 inhibits inflammatory signal transduction and could be developed as a potential anti-inflammatory agent.

Anti-Inflammatory Effects of the Novel PIM Kinase Inhibitor KMU-470 in RAW 264.7 Cells through the TLR4-NF-κB-NLRP3 Pathway.

PIM kinases, a small family of serine/threonine kinases, are important intermediates in the cytokine signaling pathway of inflammatory disease. In this study, we investigated whether the novel PIM kinase inhibitor KMU-470, a derivative of indolin-2-one, inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 cells. We demonstrated that KMU-470 suppressed the production of nitric oxide and inducible nitric oxide synthases that are induced by LPS in RAW 264.7 cells. Furthermore, KMU-470 inhibited LPS-induced up-regulation of TLR4 and MyD88, as well as the phosphorylation of IκB kinase and NF-κB in RAW 264.7 cells. Additionally, KMU-470 suppressed LPS-induced up-regulation at the transcriptional level of various pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6. Notably, KMU-470 inhibited LPS-induced up-regulation of a major component of the inflammasome complex, NLRP3, in RAW 264.7 cells. Importantly, PIM-1 siRNA transfection attenuated up-regulation of NLRP3 and pro-IL-1ß in LPS-treated RAW 264.7 cells. Taken together, these findings indicate that PIM-1 plays a key role in inflammatory signaling and that KMU-470 is a potential anti-inflammatory agent.

Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009-2014.

BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14-.44) or influenza virus (HR, 0.52; 95% CI, .38-.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062-.093), while men with influenza virus-positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.

13 Reasons Why: Viewing Patterns and Perceived Impact Among Youths at Risk of Suicide.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p<0.001). Youths with more depressive symptoms and suicidal ideation were more likely to identify with the lead characters and report negative affect while viewing. CONCLUSIONS: 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.