Digital conversations about suicide among teenagers and adults with epilepsy: A big-data, machine learning analysis.

OBJECTIVE: Digital media conversations can provide important insight into the concerns and struggles of people with epilepsy (PWE) outside of formal clinical settings and help generate useful information for treatment planning. Our study aimed to explore the big data from open-source digital conversations among PWE with regard to suicidality, specifically comparing teenagers and adults, using machine learning technology. METHODS: Advanced machine-learning empowered methodology was used to mine and structure open-source digital conversations of self-identifying teenagers and adults who endorsed suffering from epilepsy and engaged in conversation about suicide. The search was limited to 12 months and included only conversations originating from US internet protocol (IP) addresses. Natural language processing and text analytics were employed to develop a thematic analysis. RESULTS: A total of 222 000 unique conversations about epilepsy, including 9000 (4%) related to suicide, were posted during the study period. The suicide-related conversations were posted by 7.8% of teenagers and 3.2% of adults in the study. Several critical differences were noted between teenagers and adults. A higher percentage of teenagers are: fearful of "the unknown" due to seizures (63% vs 12% adults), concerned about social consequences of seizures (30% vs 21%), and seek emotional support (29% vs 19%). In contrast, a significantly higher percentage of adults show a defeatist ("given up") attitude compared to teenagers (42% vs 4%). There were important differences in the author's determined sentiments behind the conversations among teenagers and adults. SIGNIFICANCE: In this first of its kind big data analysis of nearly a quarter-million digital conversations about epilepsy using machine learning, we found that teenagers engage in an online conversation about suicide more often than adults. There are some key differences in the attitudes and concerns, which may have implications for the treatment of younger patients with epilepsy.

Screening for suicidality and its relation to undiagnosed psychiatric comorbidities in children and youth with epilepsy.

INTRODUCTION: Depression and anxiety are the most common psychiatric comorbidities in children and youth with epilepsy (CYE) and known to contribute to suicidality among them. However, not much is known about suicidality in CYE without established psychiatric comorbidities. Our research aimed to fill this knowledge gap and correlate this latent suicidality with screening tests for depression and anxiety. METHOD: After Institutional Review Board (IRB) approval, CYE who attended the epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and lacked established psychiatric diagnosis were enrolled. They filled out self-reported, validated scales for screening of depression, anxiety, and suicidality (Center for Epidemiological Studies Depression Scale for Children [CES-DC], Screen for Child Anxiety Related Emotional Disorders [SCARED], and Ask Suicide-Screening Questions [ASQ], respectively). Univariate descriptive statistics along with χ2 test of association and independent Student's t-test were performed for statistical analysis. RESULTS: A total of 119 (54.6% females) CYE were included in the study. Close to a third (30.2%) of CYE were positive for anxiety on SCARED, and 41.2% were positive for depression based on CSE-DC scoring. A total of 13 (10.9%) CYE indicated suicidality by answering at least one positive response on ASQ. The SCARED had a low positive correlation with the ASQ (r = 0.32) but a moderate positive correlation with the CES-DC (r = 0.64). CONCLUSION: We found that a small but significant 11% of CYE without any established psychiatric diagnosis expressed suicidality on a self-reported questionnaire. This highlights the importance of using psychiatry screening tests in all CYE. Future research using a larger, diversified cohort is needed to confirm our findings.

Ethical dilemmas in pediatric and adolescent psychogenic nonepileptic seizures.

To date, only a very narrow window of ethical dilemmas in psychogenic nonepileptic seizures (PNES) has been explored. Numerous distinct ethical dilemmas arise in diagnosing and treating pediatric and adolescent patients with PNESs. Important ethical values at stake include trust, transparency, confidentiality, professionalism, autonomy of all stakeholders, and justice. In order to further elucidate the ethical challenges in caring for this population, an ethical analysis of the special challenges faced in four specific domains is undertaken: (1) conducting and communicating a diagnosis of PNESs, (2) advising patients about full transparency and disclosure to community including patients' peers, (3) responding to requests to continue antiepileptic drugs, and (4) managing challenges arising from school policy and procedure. An analysis of these ethical issues is essential for the advancement of best care practices that promote the overall well-being of patients and their families.

Human microvascular dysfunction and apoptotic injury induced by AL amyloidosis light chain proteins.

Light chain amyloidosis (AL) involves overproduction of amyloidogenic light chain proteins (LC) leading to heart failure, yet the mechanisms underlying tissue toxicity remain unknown. We hypothesized that LC induces endothelial dysfunction in non-AL human microvasculature and apoptotic injury in human coronary artery endothelial cells (HCAECs). Adipose arterioles (n = 34, 50 ± 3 yr) and atrial coronary arterioles (n = 19, 68 ± 2 yr) from non-AL subjects were cannulated. Adipose arteriole dilator responses to acetylcholine/papaverine were measured at baseline and 1 h exposure to LC (20 µg/ml) from biopsy-proven AL subjects (57 ± 11 yr) without and with antioxidant cotreatment. Coronary arteriole dilation to bradykinin/papaverine was measured post-LC exposure. HCAECs were exposed to 1 or 24 h of LC. LC reduced dilation to acetylcholine (10(-4) M: 41.6 ± 7 vs. 85.8 ± 2.2% control, P < 0.001) and papaverine (81.4 ± 4.6 vs. 94.8 ± 1.3% control, P < 0.01) in adipose arterioles and to bradykinin (10(-6) M: 68.6 ± 6.2 vs. 90.9 ± 1.6% control, P < 0.001) but not papaverine in coronary arterioles. There was an increase in superoxide and peroxynitrite in arterioles treated with LC. Adipose arteriole dilation was restored by cotreatment with polyethylene glycol-superoxide dismutase and tetrahydrobiopterin but only partially restored by mitoquinone (mitochondria-targeted antioxidant) and gp91ds-tat (NADPH oxidase inhibitor). HCAECs exposed to LC showed reduced NO and increased superoxide, peroxynitrite, annexin-V, and propidium iodide compared with control. Brief exposure to physiological amounts of LC induced endothelial dysfunction in human adipose and coronary arterioles and increased apoptotic injury in coronary artery endothelial cells likely as a result of oxidative stress, reduced NO bioavailability, and peroxynitrite production. Microvascular dysfunction and injury is a novel mechanism underlying AL pathobiology and is a potential target for therapy.

Molecular basis for nucleotide-binding specificity: role of the exocyclic amino group "N2" in recognition by a guanylyl-ribonuclease.

Proteins interact with nucleotides to perform a multitude of functions within cells. These interactions are highly specific; however, the molecular basis for this specificity is not well understood. To identify factors critical for protein-guanine nucleotide recognition the binding of two closely related ligands, guanosine 3'-monophosphate (3'GMP) and inosine 3'-monophosphate (3'IMP), to Ribonuclease Sa (RNase Sa), a small, guanylyl-endoribonuclease from Streptomyces aureofaciens, was compared using isothermal titration calorimetry, NMR, X-ray crystallography and molecular dynamics simulations. This comparison has allowed for the determination of the contribution of the exocyclic amino group "N2" of the guanine base to nucleotide binding specificity. Calorimetric measurements indicate that RNase Sa has a higher affinity for 3'GMP (K=(1.5+/-0.2)x10(5)) over 3'IMP (K=(3.1+/-0.2)x10(4)) emphasizing the importance of N2 as a key determinant of RNase Sa guanine binding specificity. This result was unexpected as the published structural data for RNase Sa in complex with 3'GMP showed only a potential long-range interaction (>3.3A) between N2 and the side-chain of Glu41 of RNase Sa. The observed difference in affinity is largely due to a reduction in the favorable enthalpy change by 10 kJ/mol for 3'IMP binding as compared to 3'GMP that is accompanied by a significant difference in the heat capacity changes observed for binding the two ligands. To aid interpretation of the calorimetric data, the first crystal structure of a small, guanylyl ribonuclease bound to 3'IMP was determined to 2.0 A resolution. This structure has revealed small yet unexpected changes in the ligand conformation and differences in the conformations of the side-chains contacting the sugar and phosphate moieties as compared to the 3'GMP complex. The structural data suggest the less favorable enthalpy change is due to an overall lengthening of the contacts between RNase Sa and 3'IMP as compared to 3'GMP. The long-range interaction between N2 and Glu41 is critical for positioning of the nucleotide in the binding cleft for optimal contact formation. Thus, combined, the data demonstrate how a long-range interaction can have a significant impact on nucleotide binding affinity and energetics.

Development and Validation of the Gatekeeper Behavior Scale.

BACKGROUND: Community-based gatekeeper trainings are effective tools in increasing gatekeeper skills but few validated measures assess impact. AIMS: This study aimed at determining the validity of an 11-item Gatekeeper Behavior Scale (GBS) to assess gatekeeper skills that predict behavior. METHOD: To validate the scale, 8,931 users were administered GBS surveys at pretraining, posttraining, and follow-up periods. The training was one of five from the suite of online At-Risk mental health learning simulations for university faculty/staff or students or high/middle school educators. RESULTS: A confirmatory factor analysis revealed the three-factor model based on the subscales of preparedness, likelihood, and self-efficacy fit the data best. Factor loadings showed all items correlated highly with theoretical constructs (r ≥ .84, p < .001). The GBS had high internal consistency (α = 0.93). Criterion-related validity for likelihood to discuss concerns at posttraining was significantly related to approaching students believed to be in psychological distress (r = .219, p < .001). Likelihood to refer significantly correlated with the number of students referred (r = .235, p < .001). Convergent validity was established via a correlation between self-efficacy in motivating someone to seek help and general self-efficacy (r = .519, p < .001). CONCLUSION: The GBS appears to be a valid tool in measuring the impact of online gatekeeper training simulations and holds promise for assessing other delivery methods.

Adapting Childhood Comes First for children.

In the present study, an attempt was made to adopt an intervention strategy from the principles expressed in Childhood Comes First: A Crash Course in Childhood for Adults (Helfer, 1978) to address the needs of abused children in a group format. The constructs underlying the tasks which comprise the crash course were generally found to be adaptable for use with children. They are: (1) sensory training; (2) self-acceptance; (3) self-control; (4) responsibility; (5) accepting one's own feelings; and (6) relating to others. The experience of working with seven abused children in a group which met weekly for six months to address these issues is described.

Post-traumatic stress symptoms in mothers following children's reports of sexual abuse: an exploratory study.

Symptoms of post-traumatic stress disorder were assessed in mothers whose children were seen subsequent to alleged sexual abuse. Stress symptoms were commonly found among these women following the reports of abuse. Mothers who had themselves been sexually abused as children exhibited significantly more stress symptoms than did those who had not experienced such abuse in childhood.

Containing aggressive acting out in abused children.

Sixteen physically abused children participated in a 15-week intervention program. Ratings of behavior on a continuum from aggressive to cooperative were made during the program and during in-home follow-up six months later. Following an initial increase in aggressive behavior, significant increases in cooperative behavior were reported.

An independent effectiveness trial of multisystemic therapy with juvenile justice youth.

This study examines the effectiveness of an evidence-based practice, multisystemic therapy (MST), conducted in a real-world mental health setting with juvenile justice involved youth and their families. Importantly, this is the first randomized clinical trial of MST with juvenile offenders in the United States conducted without direct oversight by the model developers. This study reports outcomes achieved for 93 youth randomly assigned to MST or treatment as usual (TAU) services through 18-month follow-up posttreatment for offense data and 6-month follow-up posttreatment for ratings of the Child and Adolescent Functional Assessment Scale (CAFAS). Outcomes include significant reduction in rearrest and improvement in 4 areas of functioning measured by the CAFAS for youth who received MST. Implications for delivery of empirically supported treatments in real-world settings are discussed.

Comparing the mental health needs of female and male incarcerated juvenile delinquents.

The present study was undertaken to survey the prevalence of mental disorder in juvenile justice facilities and to compare the mental health needs for females and males. Girls displayed significantly more mental health needs than boys. The estimated prevalence of mental disorder for boys was 27%, compared with 84% for girls. The difference is highly significant and is discussed in terms of service system issues in juvenile justice that affect males and females differently.