Differential role of ventral tegmental area acetylcholine and N-methyl-D-aspartate receptors in cocaine-seeking

Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Cues evoke burst firing of ventral tegmental area (VTA) dopamine (DA) neurons and phasic DA release in the nucleus accumbens (NAc). Cholinergic and glutamatergic input to the VTA is suggested to gate phasic DA activity. However, the role of VTA cholinergic and glutamatergic receptors in regulating phasic dopamine release and cue-induced drug-seeking in cocaine experienced subjects is not known. In male Sprague-Dawley rats, we found that VTA inactivation strongly inhibited, while VTA stimulation promoted, cocaine-seeking behavior during early withdrawal. Blockade of phasic activated D1 receptors in the NAc core also strongly inhibited cue-induced cocaine-seeking--suggesting an important role of phasic DA activity in the VTA to NAc core circuit. Next, we examined the role of VTA acetylcholine receptors (AChRs) and N-methyl-D-aspartate receptors (NMDARs) in regulating both NAc core phasic DA release and cue-induced cocaine-seeking. In cocaine naïve subjects, VTA infusion of the nicotinic acetylcholine receptor (AChR) antagonist mecamylamine, the muscarinic AChR antagonist scopolamine, or the NMDAR antagonist AP-5, led to robust attenuation of phasic DA release in the NAc core. During early cocaine withdrawal, VTA infusion of AP-5 had limited effects on NAc phasic DA release and cue-induced cocaine-seeking while VTA infusion of mecamylamine or scopolamine robustly inhibited both phasic DA release and cocaine-seeking. The results demonstrate that VTA AChRs, but not NMDARs, strongly regulate cue-induced cocaine-seeking and phasic DA release during early cocaine withdrawal

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation: Jointly developed with the Society for Maternal-Fetal Medicine

The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7 and 27 6/7 weeks of gestation, with a focus on mifepristone-misoprostol and misoprostol-only regimens. We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. Several randomized trials of medication abortion between 14 0/7 and 27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low-resource settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7 and 27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation: Jointly developed with the Society for Maternal-Fetal Medicine

The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7 and 27 6/7 weeks of gestation, with a focus on mifepristone-misoprostol and misoprostol-only regimens. We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. Several randomized trials of medication abortion between 14 0/7 and 27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low-resource settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7 and 27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure

American College of Cardiology; American Heart Association Task Force; European Society of Cardiology Committee for Practice Guidelines. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death).

The purpose this document is to update and combine the previously published recommendations into one source approved by the major cardiology organizations in the United States and Europe. We have consciously attempted to create a streamlined document, not a textbook, that would be useful specifically to locate recommendations on the evaluation and treatment of patients who have or may be at risk for ventricular arrhythmias. Thus, sections on epidemiology, mechanisms and substrates, and clinical presentations are brief, because there are no recommendations for those sections. For the other sections, the wording has been kept to a minimum, and clinical presentations have been confined to those aspects relevant to forming recommendations