Duration of New-Onset Depressive Symptoms During Medical Residency.

Importance: The implications of new-onset depressive symptoms during residency, particularly for first-year physicians (ie, interns), on the long-term mental health of physicians are unknown.

Objective: To examine the association between and persistence of new-onset and long-term depressive symptoms among interns.

Design, Setting, And Participants: The ongoing Intern Health Study (IHS) is a prospective annual cohort study that assesses the mental health of incoming US-based resident physicians.

Impact of tetraplegia vs. paraplegia on venoarteriolar, myogenic and maximal cutaneous vasodilation responses of the microvasculature: Implications for cardiovascular disease.

Cardiovascular disease (CVD) is a leading cause of mortality in persons with SCI. While vascular remodeling and function after SCI is well documented, changes in the vascular structure and function are comparably understudied, but importantly predict CVD risk. Specifically, the integrity of venoarteriolar (VAR), myogenic (MYO) and maximal vasodilation responses are largely unknown after SCI, especially in persons with tetraplegia (TP) at highest risk of CVD.

Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children and Adolescents.

Objectives: Aripiprazole modulates dopaminergic and serotonergic pathways that may play a role in the pathogenesis of Tourette's disorder (TD). This trial evaluated the efficacy and safety of oral aripiprazole in the suppression of tics in children and adolescents with TD.

Methods: This phase 3, randomized, double-blind, placebo-controlled trial ( ClinicalTrials.

Early antipsychotic response to aripiprazole in adolescents with schizophrenia: predictive value for clinical outcomes.

Objective: In adults with chronic schizophrenia, most symptom decreases occur in the first few weeks of antipsychotic treatment, and nonresponse at week 2 predicts a later nonresponse. The trajectory of antipsychotic response and the predictive value of early antipsychotic effects were investigated for ultimate outcome in adolescent schizophrenia, where such data are still lacking.

Method: This post hoc analysis of a 6-week, randomized, double-blinded trial of aripiprazole (n = 196) versus placebo (n = 98) evaluated if adolescents 13 to 17 years old with schizophrenia exhibited substantial symptomatic improvement to aripiprazole in the first few treatment weeks and whether early response (ER) versus early nonresponse (ENR) predicted clinically relevant outcomes.

Hospitalisation rates in patients switched from oral anti-psychotics to aripiprazole once-monthly for the management of schizophrenia.

Objective: To report the design and preliminary results of a mirror-image study comparing total psychiatric hospitalisation rates pre- and post-switch to aripiprazole once-monthly, an extended release injectable solution.

Methods: A multi-center, open-label mirror-image study of patients (18-65 years) with schizophrenia to compare total psychiatric hospitalisation rates between retrospective treatment with oral standard-of-care (SOC) anti-psychotics and prospective treatment with aripiprazole once-monthly in a naturalistic community setting in North America. Total psychiatric hospitalisation rates were assessed between retrospective (Months -4 to -1) and prospective treatment periods (Months 4-6) for patients who completed ≥3 months aripiprazole once-monthly.

Clinical significance of treatment effects with aripiprazole versus placebo in a study of manic or mixed episodes associated with pediatric bipolar I disorder.

Objective: Published studies in adult and pediatric bipolar disorder have used different definitions of treatment response. This analysis aimed to compare different definitions of response in a large sample of children and adolescents.

Methods: Anexploratory analysis of a 4-week, multicenter, placebo-controlled study assessed patients (n=296; ages, 10-17 years) with an acute manic/mixed episode associated with BIPOLAR I disorder who were randomized to aripiprazole (10 or 30 mg/day) or placebo.

Respondent and item level patterns of response of aripiprazole in the acute treatment of pediatric bipolar I disorder.

Background: Few studies have evaluated the value of a parent- and subject-rated scale in detecting symptom change in response to pharmacologic treatment.

Methods: This was a post-hoc analysis of data from a 4-week, randomized, double-blind, placebo-controlled study to evaluate which informants detect response to treatment with aripiprazole in pediatric subjects experiencing a mixed or manic episode associated with bipolar I disorder. Efficacy assessments included clinician-rated scales and the parent- and subject-rated 10-item General Behavior Inventory Mania (GBI-M10) and Depression (GBI-D10) scales.

Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans.

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6-38 (PACAP6-38) and the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis.

Young mania rating scale line item analysis in pediatric subjects with bipolar I disorder treated with aripiprazole in a short-term, double-blind, randomized study.

Objective: The aim of this study was to evaluate the effects of aripiprazole treatment on individual Young Mania Rating Scale (YMRS) line items in pediatric subjects with manic or mixed episodes associated with bipolar I disorder to better understand the discrete symptom improvements.

Methods: This was a post hoc analysis of the YMRS line item data from a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Two hundred ninety-six eligible subjects were randomized to aripiprazole 10 mg/day (n = 98), aripiprazole 30 mg/day (n = 99), or placebo (n = 99).

Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans.

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC).

VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans.

Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6-38.

Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans.

Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased local skin temperature (Tloc) and whole body heat stress in humans. In forearm skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat stress. To explore the relative roles and interactions of these isoforms, we examined the effects of a relatively specific eNOS inhibitor, N(omega)-amino-l-arginine (LNAA), and a specific nNOS inhibitor, N(omega)-propyl-l-arginine (NPLA), both separately and in combination, on skin blood flow (SkBF) responses to increased Tloc and heat stress in two protocols.

Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo.

Nitric oxide (NO) participates in locally mediated vasodilation induced by increased local skin temperature (T(loc)) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS (eNOS) participates in the former, but not the latter, response. We tested this hypothesis by examining the effects of the eNOS antagonist N(G)-amino-l-arginine (l-NAA) on skin blood flow (SkBF) responses to increased T(loc) and whole body heat stress.

Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo.

The physiological roles of constitutively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constitutively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming.