Incidence of spontaneous arrhythmias in freely moving healthy untreated Sprague-Dawley rats.

Spontaneous arrhythmia characterization in healthy rats can support interpretation when studying novel therapies. Male (n = 55) and female (n = 40) Sprague-Dawley rats with telemetry transmitters for a derivation II ECG. Arrhythmias were assessed from continuous ECG monitoring over a period of 24-48 h, and data analyzed using an automated detection algorithm with 100% manual over-read.

Perspectives of Treatment Providers and Clients with Serious Mental Illness Regarding Effective Therapeutic Relationships.

This study explores the nature of clinical therapeutic relationships between mental health treatment providers and high-need clients with serious mental illness who had recently discontinued treatment. Semi-structured qualitative interviews of 56 clients with serious mental illness who had recently discontinued care and 25 mental health treatment providers were completed. Both clients with serious mental illness and treatment providers emphasized the importance of client-focused goal setting, time and availability of treatment providers, a caring approach, and trust and honesty in the relationship.

CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology.

This chapter describes various approaches for the preclinical assessment of drug-induced central nervous system (CNS) adverse effects. Traditionally, methods to evaluate CNS effects have consisted of observing and scoring behavioral responses of animals after drug is administered. Among several behavioral testing paradigms, the Irwin and the functional observational battery (FOB) are the most commonly used assays for the assessment of CNS effects.

In silico prediction of hERG inhibition.

The voltage-gated potassium channel encoded by hERG carries a delayed rectifying potassium current (IKr) underlying repolarization of the cardiac action potential. Pharmacological blockade of the hERG channel results in slowed repolarization and therefore prolongation of action potential duration and an increase in the QT interval as measured on an electrocardiogram. Those are possible to cause sudden death, leading to the withdrawals of many drugs, which is the reason for hERG screening.

Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists.

Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group.

Transitioning between systems of care: missed opportunities for engaging adults with serious mental illness and criminal justice involvement.

Individuals with serious mental illness are overrepresented in the criminal justice system and face difficulties accessing mental health services both during incarceration and upon re-entry into the community. This study examines how such individuals describe their experiences receiving care both during and after their time in custody and explores the perspectives of mental health service providers who treat this population upon re-entry. Semi-structured interviews were conducted with 43 individuals identified as having a history of serious mental illness and criminal justice involvement, as well as with 25 providers who have worked with this population.

Disengagement from care: perspectives of individuals with serious mental illness and of service providers.

Objective: This study sought to describe reasons for disengagement from services and practical guidelines to enhance engagement among individuals with serious mental illness and high need for treatment.

Methods: Qualitative interviews were conducted with 56 individuals with serious mental illness and 25 providers recruited from a larger project that used administrative data to identify individuals with serious mental illness who had disengaged from care. Individuals with serious mental illness and providers described reasons for disengagement and effective provider engagement strategies.

It's good to know: how treatment knowledge and belief affect the outcome of distant healing intentionality for arthritis sufferers.

Objective: This small-scale study explores the role of expectancy in response to distant healing by testing two hypotheses: 1) Participants aware of placement in the healing condition will report greater relief than those aware they are not receiving distant healing; 2) Participants who express belief in distant healing will report greater relief than those expressing disbelief.

Methods: Sixty patients were recruited from a rheumatology outpatient clinic, and through online support networks and blogs. Participants were randomly allocated to one of four conditions, those in the healing condition received distant healing from self-reported healers, while participants in the control condition received no intervention.

Approaches to seizure risk assessment in preclinical drug discovery.

Assessment of seizure risk traditionally occurs late in the drug discovery process using low-throughput, resource intensive in vivo assays. Such approaches do not allow sufficient time to mitigate risk by influencing chemical design. Early identification using cheaper, higher throughput assays with lower animal and compound requirements would be preferable.

Recombinant GABA(B) receptors formed from GABA(B1) and GABA(B2) subunits selectively inhibit N-type Ca(2+) channels in NG108-15 cells.

Efficient transfection of NG108-15 cells with GABA(B) receptor subunits was achieved using polyethylenimine. Baclofen modulated high voltage-activated Ca(2+) current in differentiated cells transfected with GABA(B1) and GABA(B2) receptor subunits or with the GABA(B2) subunit alone, but not with the GABA(B1) subunit alone. Characteristics of the current modulation were very similar for cells transfected with GABA(B1/2) and GABA(B2) subunits.