Factors Contributing to the Utilization of Adult Mental Health Services in Children and Adolescents Diagnosed with Hyperkinetic Disorder

Objectives. To examine whether age of First diagnosis, gender, psychiatric comorbidity, and treatment modalities (pharmacotherapy or psychotherapy) at Child and Adolescent Mental Health Services (CAMHS) moderate the risk of Adult Mental Health Services (AMHS) utilization in patients diagnosed with hyperkinetic disorder at CAMHS. Methods. Data were derived from the Madrid Psychiatric Cumulative Register Study. The target population comprised 32,183 patients who had 3 or more visits at CAMHS. Kaplan-Meier curves were used to assess survival data. A series of logistic regression analyses were performed to study the role of age of diagnosis, gender, psychiatric comorbidity, and treatment modalities. Results. 7.1% of patients presented with hyperkinetic disorder at CAMHS. Compared to preschool children, children and adolescents first diagnosed with hyperkinetic disorder at CAMHS were more likely to use AMHS. Female gender and comorbidity with affective disorders, schizophrenia, schizotypal and delusional disorders increased the risk of use of AMHS. Pharmacological or combined treatment of hyperkinetic disorder diagnosed at CAMHS was associated with increased risk of use at AMHS. Conclusions. Older age of first diagnosis, female gender, psychiatric comorbidity, and pharmacological treatment at CAMHS are markers of risk for the transition from CAMHS to AMHS in patients with hyperkinetic disorder diagnosed at CAMHS

Defining the Role of SOX17 in Human Hematopoietic Development

The transcriptional regulators that govern the generation of hematopoietic stem cells (HSCs) from hemogenic endothelial cells (HECs) during human definitive hematopoiesis have not been identified. Based on findings from studies in the mouse, we hypothesized that the transcription factor SOX17 plays a pivotal role in the establishment of the definitive, but not the primitive hematopoietic program generated from human pluripotent stem cells (hPSCs) differentiated in culture. We observed that SOX17 was expressed within definitive CD34+ ‘HECs’ and emerging definitive, but not primitive, CD43+ hematopoietic cells. Detailed analyses showed that expression of SOX17 was downregulated as CD34+ HECs differentiate and undergo an endothelial-to-hematopoietic transition (EHT) to acquire a hematopoietic fate. This transition from a SOX17+ to a SOX17– population was blocked using a NOTCH signaling inhibitor. Despite the expression of SOX17 in definitive progenitors, the loss of SOX17 had no effect on definitive or primitive hematopoiesis in the hPSC differentiation cultures.M.Sc

Age of First Suicide Attempt in Men and Women: An Admixture Analysis

Objectives. To define different subgroups of suicide attempters according to age at onset of suicide attempts. Methods. Participants were 229 suicide attempters (147 females; 82 males) admitted to a general hospital in Madrid, Spain. We used admixture analysis to determine the best-fitting model for the age at onset of suicide attempts separated by sex. Results. The best fitted model for the age at onset of suicide attempts was a mixture of two gaussian distributions. Females showed an earlier age at onset of suicide attempts in both Gaussian distributions (mean ± S.D.) (26.98 ± 5.69 and 47.98 ± 14.13) than males (32.77 ± 8.11 and 61.31 ± 14.61). Early-onset female attempters were more likely to show borderline personality disorder than late-onset female attempters (OR = 11.11; 95% CI = 2.43-50.0). Conclusions. Age at onset of suicide attempts characterizes different subpopulations of suicide attempters

Age of First Suicide Attempt in Men and Women: An Admixture Analysis

Objectives. To define different subgroups of suicide attempters according to age at onset of suicide attempts. Methods. Participants were 229 suicide attempters (147 females; 82 males) admitted to a general hospital in Madrid, Spain. We used admixture analysis to determine the best-fitting model for the age at onset of suicide attempts separated by sex. Results. The best fitted model for the age at onset of suicide attempts was a mixture of two gaussian distributions. Females showed an earlier age at onset of suicide attempts in both Gaussian distributions (mean ± S.D.) (26.98 ± 5.69 and 47.98 ± 14.13) than males (32.77 ± 8.11 and 61.31 ± 14.61). Early-onset female attempters were more likely to show borderline personality disorder than late-onset female attempters (OR = 11.11; 95% CI = 2.43–50.0). Conclusions. Age at onset of suicide attempts characterizes different subpopulations of suicide attempters

Ibrutinib Displays Atrial-Specific Toxicity in Human Stem Cell-Derived Cardiomyocytes

Summary: Ibrutinib (IB) is an oral Bruton's tyrosine kinase (BTK) inhibitor that has demonstrated benefit in B cell cancers, but is associated with a dramatic increase in atrial fibrillation (AF). We employed cell-specific differentiation protocols and optical mapping to investigate the effects of IB and other tyrosine kinase inhibitors (TKIs) on the voltage and calcium transients of atrial and ventricular human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). IB demonstrated direct cell-specific effects on atrial hPSC-CMs that would be predicted to predispose to AF. Second-generation BTK inhibitors did not have the same effect. Furthermore, IB exposure was associated with differential chamber-specific regulation of a number of regulatory pathways including the receptor tyrosine kinase pathway, which may be implicated in the pathogenesis of AF. Our study is the first to demonstrate cell-type-specific toxicity in hPSC-derived atrial and ventricular cardiomyocytes, which reliably reproduces the clinical cardiotoxicity observed. : The authors employ cell-specific cardiac differentiation protocols, RNA-seq, and optical mapping to demonstrate atrial-specific toxicity of ibrutinib, a first-in-class BTK inhibitor. Other tyrosine kinase inhibitors (TKIs) with the same drug target do not affect atrial electrophysiology. Nilotinib and vandetanib, two TKIs known to be associated with QT prolongation and risk of sudden death, demonstrated ventricular-specific electrophysiologic dysregulation. Keywords: cardiac electrophysiology, tyrosine kinase inhibitors, atrial fibrillation, drug screening, optical mapping, RNA-se

Distinguishing the relevant features of frequent suicide attempters

In spite of the high prevalence of suicide behaviours and the magnitude of the resultant burden, little is known about why individuals reattempt. We aim to investigate the relationships between clinical risk factors and the repetition of suicidal attempts