A research agenda for gender and substance use disorders in the emergency department.

For many years, gender differences have been recognized as important factors in the etiology, pathophysiology, comorbidities, and treatment needs and outcomes associated with the use of alcohol, drugs, and tobacco. However, little is known about how these gender-specific differences affect ED utilization; responses to ED-based interventions; needs for substance use treatment and barriers to accessing care among patients in the ED; or outcomes after an alcohol-, drug-, or tobacco-related visit. As part of the 2014 Academic Emergency Medicine consensus conference on "Gender-Specific Research in Emergency Care: Investigate, Understand and Translate How Gender Affects Patient Outcomes," a breakout group convened to generate a research agenda on priority questions related to substance use disorders.

Ischemic stroke presenting as fluctuating focal weakness in an otherwise healthy young man.

A 32-year-old man presented to our emergency department (ED) with no complaints after paramedics responded to a fall. Medics noted left-sided weakness on scene. Symptoms were initially absent in the ED, although later recurred, and included dramatically waxing and waning focal weakness. An acute middle cerebral artery ischemic stroke was diagnosed, and tissue plasminogen activator was administered. Despite a fluctuating course of symptoms, our patient ultimately achieved a complete recovery.

Mental health and emergency medicine: a research agenda.

The burden of mental illness is profound and growing. Coupled with large gaps in extant psychiatric services, this mental health burden has often forced emergency departments (EDs) to become the de facto primary and acute care provider of mental health care in the United States. An expanded emergency medical and mental health research agenda is required to meet the need for improved education, screening, surveillance, and ED-initiated interventions for mental health problems. As an increasing fraction of undiagnosed and untreated psychiatric patients passes through the revolving doors of U.S. EDs, the opportunities for improving the art and science of acute mental health care have never been greater. These opportunities span macroepidemiologic surveillance research to intervention studies with individual patients. Feasible screening, intervention, and referral programs for mental health patients presenting to general EDs are needed. Additional research is needed to improve the quality of care, including the attitudes, abilities, interests, and virtues of ED providers. Research that optimizes provider education and training can help academic settings validate psychosocial issues as core components and responsibilities of emergency medicine. Transdisciplinary research with federal partners and investigators in neuropsychiatry and related fields can improve the mechanistic understanding of acute mental health problems. To have lasting impact, however, advances in ED mental health care must be translated into real-world policies and sustainable program enhancements to assure the uptake of best practices for ED screening, treatment, and management of mental disorders and psychosocial problems.

Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients.

Intoxicating concentrations of ethanol inhibit N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation, an interaction thought to underlie a major component of the central nervous system actions of ethanol. Another form of synaptic potentiation involving activation of L-type dihydropyridine-sensitive voltage-gated calcium channels (VGCCs) has been described, but very little information concerning ethanol effects on VGCC-dependent synaptic potentiation is available. Here, we assessed ethanol effects on VGCC-dependent synaptic potentiation using whole cell patch-clamp recordings of alpha-amino-3-hydroxy-5-methyl-4-soxazolepropionic acid (AMPA) receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in area CA1 of the rat hippocampus. No potentiation was observed in artificial cerebrospinal fluid containing 2 to 3 mM Ca2+, but marked potentiation of mEPSCs was consistently observed in 4 mM Ca2+ and with patch pipettes containing an ATP-regenerating system. This potentiation was insensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid, whereas it was completely blocked the L-type VGCC antagonist nifedipine. Potentiation was also blocked dose dependently by bath application of ethanol (25-75 mM), which had no effect on baseline mEPSC amplitude or frequency. The synaptic potentiation involved enhancement of both presynaptic and postsynaptic components because significant increases in both the frequency and amplitude of AMPA mEPSCs were observed. Ethanol inhibition of VGCC-dependent synaptic potentiation seemed to occur at the induction step because both the increases in mEPSC frequency and amplitude were affected. To address that question more directly, we used fluorescent imaging of synaptically evoked dendritic calcium events, which displayed a similarly marked ethanol sensitivity. Thus, ethanol modulates fast excitatory synaptic transmission by inhibiting the induction of an NMDA receptor-independent form of synaptic potentiation observed at excitatory synapses on central neurons.

Ifenprodil and ethanol enhance NMDA receptor-dependent long-term depression.

Long-term alterations in synaptic transmission are thought to underlie various types of alcohol-related brain disorders. While ethanol effects on synaptic potentiation are well documented, ethanol effects on synaptic depression have not been addressed. Herein, we performed experiments to assess the role of ethanol on long-term depression (LTD) formation. In rat hippocampal slices, prolonged low-frequency stimulation (LFS) of CA1 Schaffer collaterals (1 Hz for 7 min) induced saturable, long-lasting, reversible N-methyl-D-aspartate (NMDA) receptor-dependent LTD of stimulus-evoked dendritic population excitatory postsynaptic potentials. This depression (-26% LTD amplitude) was observed in young rats (12-20 days old), but not adult rats (28-35 days old). Induction of LTD was blocked (-3% LTD amplitude) when the LFS was delivered in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid. When the conditioning LFS was delivered in the presence of ethanol, there was a significant enhancement in the induction of NMDA receptor-dependent LTD versus control LTD (-36% LTD amplitude). Ifenprodil, an N-methyl-D-aspartate receptor subunit 2B (NR2B)-selective antagonist, also significantly facilitated the induction of LTD (-40% LTD amplitude). Consistent with this result, ifenprodil did not affect the NMDA receptor-dependent component of the baseline synaptic response, whereas D-2-amino-5-phosphonovaleric acid caused significant depression of the NMDA component. These data indicate that whereas ethanol is known to inhibit NMDA receptor function in a variety of systems, it significantly enhances the induction of NMDA receptor-dependent LTD. Furthermore, since ifenprodil is known to select for ethanol-sensitive subtypes of NR2B-NMDA receptors, these data also suggest that NR2B-containing NMDA receptor subpopulations do not contribute to LTD, but instead may actually play inhibitory roles in LTD induction.