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This randomized, noninferiority trial compared ketamine with electroconvulsive therapy in treatment-resistant depression. Ketamine was noninferior to ECT for treatment-resistant depression without psychosis.

Scaling Up Point-of-Care Fentanyl TestingAlthough fentanyl is now the dominant driver of the U.S. opioid epidemic, our health care system has struggled to adapt toxicology screening practices to this reality.

Neuroinflammation plays a central role in the neuropathogenesis of a wide-spectrum of neurologic and psychiatric disease, but current neuroimaging methods to detect and characterize neuroinflammation are limited. We explored the sensitivity of quantitative multi-compartment diffusion MRI, and specifically neurite orientation dispersion and density imaging (NODDI), to detect changes in microglial density in the brain. Monte Carlo simulations of water diffusion using a NODDI acquisition scheme were performed to measure changes in a virtual MRI signal following modeled cellular changes within the extra-neurite space. 12-week-old C57BL/6J male mice ( = 48; 24 control, 24 treated with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622) were sacrificed at 0, 1, 3, and 7 days following withdrawal of CSF1R inhibition and were imaged to obtain measures of the orientation dispersion index (ODI). Following imaging, all brains were immunostained with Iba-1, NeuN, and GFAP for quantitative fluorescence microscopy. Cell populations were calculated with the ImageJ particle analyzer tool; correlation between microglial density and mean ODI values were calculated with Kendall's tau. Monte Carlo simulations demonstrate the sensitivity and positive correlation of ODI to increased occupancy in the extra-neurite space. Commensurate with our simulation data, NODDI imaging demonstrates an increase in ODI as microglia repopulate the brain following the withdrawal of CSF1R inhibition. Quantitative immunofluorescence of microglial density reveals that microglial density is positively correlated with ODI and greater hindered diffusion in the extra-neurite space (τ = 0.386, < 0.05). Our results demonstrate that clinically feasible multi-compartment diffusion weighted imaging techniques such as NODDI are sensitive to microglial density and the cellular changes associated with microglial activation and highlights its potential to improve clinical diagnostic accuracy, patient risk stratification, and therapeutic monitoring of neuroinflammation in neurologic and psychiatric disease.

Growing evidence from observational studies and clinical trials suggests that psychedelics such as lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, and psilocybin may hold treatment potential for alcohol, opioid, tobacco, and other substance use disorders (SUDs). The mechanisms by which psychedelics might exert therapeutic efficacy in these conditions have not been fully elucidated, although the subjective effects of the psychedelic experience appear necessary. Given the often profound nature of psychedelic experiences, they may serve as turning points in the life narratives of users, eliciting lasting behavioral change. To better characterize the extent of psychedelics' therapeutic potential in patients with SUDs, randomized, placebo-controlled trials are needed, with some already underway. However, even if such trials demonstrate compelling evidence of psychedelics' therapeutic potential, these substances may still face considerable challenges to integration into the current SUDs treatment paradigm because of clinician concerns about their addictive potential and philosophical objections from 12-step facilitation programs. [Psychiatr Ann. 2022;52(9):365–370.]

Rationale There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs. Objectives This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States. Methods The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics. Results Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated. Conclusions Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts.

One of the most disheartening aspects ofthe decades-long increase in drug-related harm in the United States is our failure to fully implement the wide array of effective interventions available for reducing that harm. These strategies include broad access to opioid agonist therapy,1 sterile injection supplies,2 and naloxone,3 as well as the establishment of supervised consumption sites.4 Despite their efficacy, scaling up these interventions has proven a persistent challenge as a result of poorly targeted funding, legal barriers, stigma, and inadequate coordination among stakeholders.Consequently, thousands in the United States die from drug-related overdoses and contract infectious bloodborne diseases each year, despite the preventable nature of much of this morbidity and mortality; in 2019, 70 630 people died of drug overdoses.5 As of 2010, more than 140 000 people had contracted HIV through injection drug use, and in 2011,43126 of every 100 000 people between 40 and 65 years of age who injected drugs were infected with hepatitis C virus.6 A lack of access to sterile syringes helped drive the annual incidence of acute hepatitis C virus infection from 0.3 to 0.7 cases per 100 000 people between 2004 and 20147 and has also contributed to outbreaks of hepatitis A virus and HIV in multiple states in recent years.

Lunasin is a peptide derived from the soybean 2S albumin seed protein that has both anticancer and anti-inflammatory activities. Large-scale animal studies and human clinical trials to determine the efficacy of lunasin in vivo have been hampered by the cost of synthetic lunasin and the lack of a method for obtaining gram quantities of highly purified lunasin from plant sources. The goal of this study was to develop a large-scale method to generate highly purified lunasin from defatted soy flour. A scalable method was developed that utilizes the sequential application of anion-exchange chromatography, ultrafiltration, and reversed-phase chromatography. This method generates lunasin preparations of >99% purity with a yield of 442 mg/kg defatted soy flour. Mass spectrometry of the purified lunasin revealed that the peptide is 44 amino acids in length and represents the original published sequence of lunasin with an additional C-terminal asparagine residue. Histone-binding assays demonstrated that the biological activity of the purified lunasin was similar to that of synthetic lunasin. This study provides a robust method for purifying commercial-scale quantities of biologically-active lunasin and clearly identifies the predominant form of lunasin in soy flour. This method will greatly facilitate the development of lunasin as a potential nutraceutical or therapeutic anticancer agent.

Background The conditions of diminished ovarian reserve and primary ovarian insufficiency, characterized by poor fertility outcomes, currently comprise a major challenge in reproductive medicine, particularly in vitro fertilization. Currently in the IVF industry, blastocyst developmental success rate per treatment is routinely overlooked when a live birth results from treatment. Limited data are available on this significant and actionable variable of blastocyst development optimization, which contributes to improvement of treatment success Women with elevated basal FSH concentration are reported to still achieve reasonable pregnancy rates, although only a few studies report correlations with blastocysts development. Diagnostic values of AMH/basal FSH concentrations can be useful for determining the optimal stimulation protocol as well as identification of individuals who will not benefit from IVF due to poor prognosis. The objective of this study is to identify actionable clinical and culture characteristics of IVF treatment that influence blastocyst developmental rate, with the goal of acquiring optimal success. Methods and findings A retrospective observational study was performed, based on 106 women undergoing IVF, regardless of prognosis, over a six-month period from January 1, 2015 to June 31, 2015. Rate of high-quality blastocyst production, which can be used for embryo transfer or vitrification, per normally fertilized oocyte, was evaluated. Treatment was determined successful when outcome was ≥ 40% high-quality blastocysts. The data were initially evaluated with the Evtree algorithm, a statistical computational analysis which is inspired by natural Darwinian evolution incorporating concepts such as mutation and natural selection (see Supplementary Material). The analysis processes all variables simultaneously against the outcome, aiming to maximize discrimination of each variable to then create a “branch” of the tree which can be used as a decision in treatment. The final model results in only those variables which are significant to outcomes. Generalized linear model (GLM) employing logistic regression and survival analysis with R software was used and the final fitting of the model was determined through the use of random forest and evolutionary tree algorithms. Individuals presenting with an [AMH] of >3.15 ng/ml and a good prognosis had a lower success per treatment (n = 11, 0% success) when total gonadotropin doses were greater than 3325 IU. Individuals that presented with an [AMH] of <1.78 ng/ml and a poor prognosis exhibited a greater success per treatment (n = 11, 80% success). AMH emerged as a superior indicator of blastocyst development compared to basal FSH. The accuracy of the prediction model, our statistical analysis using decision tree, evtree methodology is 86.5% in correctly predicting outcome based on the significant variables. The likelihood that the outcome with be incorrect of the model, or the error rate is 13.5%. Conclusions [AMH] is a superior indicator of ovarian stimulation response and an actionable variable for stimulation dose management for optimizing blastocyst development in culture. Women whose [AMH] is ≥3.2 mg/ml, having a good prognosis, and developing >12 mature follicles result in <40% blastocysts when gonadotropin doses exceed 3325 IU per treatment. IVF treatments for poor responders that present with infertility due to diminished ovarian reserve, if managed appropriately, can produce more usable blastocyst per IVF treatment, thus increasing rate of blastocyst developmental success and ultimately increasing live birth rates. Future studies are needed to investigate the intra-follicular and the intra-cellular mechanisms that lead to the inverse relationship of blastocysts development and total gonadotropin doses in good responders in contrast to poor responders.

Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.