The Case Against "Excited Delirium".

ABSTRACT: Citizens' deaths in police custody are sometimes attributed to "excited delirium syndrome" (ExDS). This terminology is rejected by the American Medical Association and the American Psychiatric Association. ExDS has no demonstrable pathology but has been proposed as predisposing to sudden death, thus exonerating police. Ketamine use during arrests complicates manner of death. ExDS deaths trigger lawsuits claiming police misconduct and excessive force. Defendant officers and municipalities have used ExDS to distance themselves from liability, using expert testimony from nonpsychiatrists. This argument is expressed despite lack of autopsy findings, the false idea that mental illness itself can lead to sudden death, and the absence of consistent diagnostic criteria. This article traces the history of ExDS and reviews the arguments for and against its use in psychiatry and law enforcement. The authors conclude that the label is medically unreliable, has eroded confidence in police-citizen interactions, and obscures dynamics of deaths in custody.

Involuntary Administration of Long-Acting Injectable Antipsychotics for Competency Restoration.

In implementing the decisions in the landmark case Sell v. United States, jurisdictions have adopted mechanisms for the involuntary medication of defendants to restore competency to stand trial. These procedures attempt to balance the liberty and privacy rights of the accused against the government's responsibility to ensure timely prosecution and fair trial. The question of which medications are most appropriate for this goal, however, remains open. This article reviews the legal status of the administration of long-acting injectable (LAI) antipsychotics for sustained competency restoration. We explore case law and discuss the theoretical and empirical benefits and drawbacks to this practice, considering recent technological advancements in LAI development. Some courts have regarded LAI use pursuant to Sell as equivalent or superior to immediate-acting medications, whereas others have regarded LAIs as either more intrusive or medically riskier. We conclude that the use of LAIs may be carefully integrated into treatment plans to restore and maintain trial competency amid competing interests.

Integrated omics approaches to characterize a nuclear receptor corepressor-associated histone deacetylase in mouse skeletal muscle.

Nuclear receptors regulate gene expression by differentially binding to coactivators or corepressors in a ligand-dependent manner, which further recruits a set of epigenome-modifying enzymes that remodel chromatin conformation. Histone acetylation is a major epigenomic change controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC3 is the only HDAC that confers the enzymatic activity to the complexes nucleated by nuclear receptor corepressors NCoR and SMRT. To address the metabolic function of HDAC3, we have deleted it specifically in mouse skeletal muscles. We have performed the following omics profiling in skeletal muscles of these mice: (1) RNA-seq profiling of total RNA; (2) Global nuclear run-on (GRO-seq) analysis of nascent RNAs; (3) Chromatin immuno-precipitation (ChIP-seq) of HDAC3 at both early evening and early morning; (4) proteomics profiling with mass spectrometry; (5) snap-shot metabolomics profiling of water-soluble metabolites at the basal condition; (6) snap-shot metabolomics profiling of lipid species at the basal condition; (7) kinetic fluxomics analysis of glucose utilization using 13C6-glucose In vivo during treadmill running exercise. These approaches have provided several novel insights into how nuclear receptors regulate circadian rhythm of skeletal muscle fuel metabolism, which has been published elsewhere. Here we present the original datasets and technical details during the execution, analysis, and interpretation of these omics studies.

Deletion of histone deacetylase 3 in adult beta cells improves glucose tolerance via increased insulin secretion.

OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic ß-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in ß-cells of adult mice. METHODS: An HDAC3 ß-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system. Induction of HDAC3 deletion was initiated at 8 weeks of age with administration of tamoxifen in corn oil (2 mg/day for 5 days). Mice were assayed for glucose tolerance, glucose-stimulated insulin secretion, and islet function 2 weeks after induction of the knockout. Transcriptional functions of HDAC3 were assessed by ChIP-seq as well as RNA-seq comparing control and ß-cell knockout islets. RESULTS: HDAC3 ß-cell specific knockout (HDAC3ßKO) did not increase total pancreatic insulin content or ß-cell mass. However, HDAC3ßKO mice demonstrated markedly improved glucose tolerance. This improved glucose metabolism coincided with increased basal and glucose-stimulated insulin secretion in vivo as well as in isolated islets. Cistromic and transcriptomic analyses of pancreatic islets revealed that HDAC3 regulates multiple genes that contribute to glucose-stimulated insulin secretion. CONCLUSIONS: HDAC3 plays an important role in regulating insulin secretion in vivo, and therapeutic intervention may improve glucose homeostasis.