Colorimetric Detection of Sulfur Mustard with 4-(p-Nitrobenzyl)pyridine and Its Derivatives.

In this study, we present a simple, highly sensitive, and selective colorimetric method for detecting sulfur mustard (SM) and its simulants. This method relies on a nucleophilic substitution reaction between derivatives of 4-(p-nitrobenzyl)pyridine (NBP) and SM and subsequent treatment with an external base, resulting in a visible response. This reaction exhibits an impressively low detection threshold by the naked eye, as low as 10 ppm at room temperature. In contrast to the conventional use of NBP for detecting other alkylating agents, such as nitrogen mustard, our approach eliminates the need for prolonged heating or intricate extraction processes. Both computational and experimental investigations underscore the significance of water within our detection medium as it stabilizes crucial episulfonium cation intermediates. Furthermore, we demonstrate the practical applicability of this sensor by incorporating it onto cellulose and silica surfaces, which may provide guidance for the design and development of solid-state SM detectors.

National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.

Women's professional development programs for emergency physicians: A scoping review.

Background: Gender disparities in emergency medicine (EM) persist, with women underrepresented in leadership positions and faced with unique challenges, such as gender discrimination and harassment. To address these issues, professional development programs for women have been recommended. Objectives: The purpose of this scoping review was to examine current women's professional development programs for EM and develop a collection of program characteristics, meeting topics, and tips for success that can be useful to new or existing women's professional development programs. Methods: The authors systematically searched research databases for literature detailing current women's professional development programs for EM physicians. Studies detailing professional development programs for female physicians in EM were included. Results: After 149 unique articles were screened, 11 studies met inclusion criteria, describing 10 professional development programs for women in EM. The most commonly cited program objectives included providing mentors and role models (n = 9, 90%), offering career advice and promoting professional advancement and leadership skills (n = 5, 50%), increasing academic recognition for women (n = 4, 40%), and promoting work-life balance and integration (n = 2, 20%). The most common topics covered in program sessions included mentorship and coaching, compensation and/or negotiation, leadership skills, and career advancement and promotion. Challenges and barriers to the success of these programs included a lack of funding and support, difficulty in recruiting participants, lack of institutional recognition and support, lack of time, and difficulty in sustaining the program over time. Conclusions: The study's findings can inform the development of programs that promote gender equity and support the advancement of women in EM.

A Decade in Review: Trends in Female Authorship in Peer-Reviewed Toxicology Journals.

BACKGROUND: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. RESEARCH QUESTIONS: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? METHODS: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). RESULTS: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. CONCLUSIONS: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts.

Self-reported Xylazine Experiences: A Mixed-methods Study of Reddit Subscribers.

OBJECTIVES: Xylazine is an α 2 -agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from people who use drugs (PWUDs). Specifically, we sought to answer the following: (1) What are the demographics of Reddit subscribers reporting exposure to xylazine? (2) Is xylazine a desired additive? And (3) what adverse effects of xylazine are PWUDs experiencing? METHODS: Natural language processing (NLP) was used to identify mentions of "xylazine" from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022. RESULTS: Seventy-six posts were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. Sixty-one participants completed the survey. Of those who disclosed their location, 25 of 50 participants (50%) reported locations in the Northeastern United States. The most common route of xylazine use was intranasal use (57%). Thirty-one of 59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%). CONCLUSIONS: Among respondents on these Reddit forums, xylazine seems to be an unwanted adulterant. People who use drugs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This seemed to be more common in the Northeast.

Barriers to opioid use disorder treatment: A comparison of self-reported information from social media with barriers found in literature.

Introduction: Medications such as buprenorphine and methadone are effective for treating opioid use disorder (OUD), but many patients face barriers related to treatment and access. We analyzed two sources of data-social media and published literature-to categorize and quantify such barriers. Methods: In this mixed methods study, we analyzed social media (Reddit) posts from three OUD-related forums (subreddits): r/suboxone, r/Methadone, and r/naltrexone. We applied natural language processing to identify posts relevant to treatment barriers, categorized them into insurance- and non-insurance-related, and manually subcategorized them into fine-grained topics. For comparison, we used substance use-, OUD- and barrier-related keywords to identify relevant articles from PubMed published between 2006 and 2022. We searched publications for language expressing fear of barriers, and hesitation or disinterest in medication treatment because of barriers, paying particular attention to the affected population groups described. Results: On social media, the top three insurance-related barriers included having no insurance (22.5%), insurance not covering OUD treatment (24.7%), and general difficulties of using insurance for OUD treatment (38.2%); while the top two non-insurance-related barriers included stigma (47.6%), and financial difficulties (26.2%). For published literature, stigma was the most prominently reported barrier, occurring in 78.9% of the publications reviewed, followed by financial and/or logistical issues to receiving medication treatment (73.7%), gender-specific barriers (36.8%), and fear (31.5%). Conclusion: The stigma associated with OUD and/or seeking treatment and insurance/cost are the two most common types of barriers reported in the two sources combined. Harm reduction efforts addressing barriers to recovery may benefit from leveraging multiple data sources.

Opioid overdoses involving xylazine in emergency department patients: a multicenter study.

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Self-reported Xylazine Experiences: A Mixed Methods Study of Reddit Subscribers.

Objectives: Xylazine is an alpha-2 agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from People Who Use Drugs (PWUDs). Specifically, we sought to answer the following: 1) what are the demographics of Reddit subscribers reporting exposure to xylazine? 2) is xylazine a desired additive? and 3) what adverse effects of xylazine are PWUDs experiencing? Methods: Natural Language Processing (NLP) was used to identify mentions of "xylazine" from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022. Results: 76 posts mentioning xylazine were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. 61 participants completed the survey. Of those that disclosed their location, 25/50 (50%) participants reported locations in the Northeastern United States. The most common eoute of xylazine use was intranasal use (57%). 31/59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%). Conclusions: Among respondents on these Reddit forums, xylazine appears to be an unwanted adulterant. PWUDs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This appeared to be more common in the Northeast.

Investigating the mechanism of Ni-mediated trifluoromethylthiolation of aryl halides using AgSCF3.

The mechanism of the Ni-catalysed trifluoromethylthiolation of aryl chlorides using AgSCF3 is studied herein. A variety of IPr NiII complexes were synthesized via oxidative addition of Ni0 to 2-(2-chloro)phenylpyridines. Their reactivity with AgSCF3 was tested by performing stoichiometric experiments, cyclic voltammetry, and NMR spectroscopic studies. CuSCF3 was shown to behave similarly to AgSCF3, while reactions with NMe4SCF3 revealed a major stoichiometric side reaction that forms a nickel fluoride complex. NMR kinetic studies revealed there is little correlation between the electron-withdrawing/donating nature of the para substituents on either the phenyl or pyridyl groups with the formation of the corresponding products. Cyclic voltammetry (CV) indicated the feasibilty of NiI/NiIII transitions, and an increased rate of formation of product was observed with increased solvent polarity. Evidence suggests that the mechanism proceeds via inner-sphere electron transfer (ET) from AgSCF3 to NiII, ultimately leading to the formation of the trifluoromethylthiolated product.

Can accurate demographic information about people who use prescription medications nonmedically be derived from Twitter?

Traditional substance use (SU) surveillance methods, such as surveys, incur substantial lags. Due to the continuously evolving trends in SU, insights obtained via such methods are often outdated. Social media-based sources have been proposed for obtaining timely insights, but methods leveraging such data cannot typically provide fine-grained statistics about subpopulations, unlike traditional approaches. We address this gap by developing methods for automatically characterizing a large Twitter nonmedical prescription medication use (NPMU) cohort (n = 288,562) in terms of age-group, race, and gender. Our natural language processing and machine learning methods for automated cohort characterization achieved 0.88 precision (95% CI:0.84 to 0.92) for age-group, 0.90 (95% CI: 0.85 to 0.95) for race, and 94% accuracy (95% CI: 92 to 97) for gender, when evaluated against manually annotated gold-standard data. We compared automatically derived statistics for NPMU of tranquilizers, stimulants, and opioids from Twitter with statistics reported in the National Survey on Drug Use and Health (NSDUH) and the National Emergency Department Sample (NEDS). Distributions automatically estimated from Twitter were mostly consistent with the NSDUH [Spearman r: race: 0.98 (P < 0.005); age-group: 0.67 (P < 0.005); gender: 0.66 (P = 0.27)] and NEDS, with 34/65 (52.3%) of the Twitter-based estimates lying within 95% CIs of estimates from the traditional sources. Explainable differences (e.g., overrepresentation of younger people) were found for age-group-related statistics. Our study demonstrates that accurate subpopulation-specific estimates about SU, particularly NPMU, may be automatically derived from Twitter to obtain earlier insights about targeted subpopulations compared to traditional surveillance approaches.

Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5' to 3' degradation.

Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single-molecule imaging, we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3' ends in P-bodies in the early embryo, consistent with 5' to 3' degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage.

Synthesis of 2-arylpyridines by the Suzuki-Miyaura cross-coupling of PyFluor with hetero(aryl) boronic acids and esters.

The Suzuki-Miyaura cross-coupling of pyridine-2-sulfonyl fluoride (PyFluor) with hetero(aryl) boronic acids and pinacol boronic esters is reported. The reactions can be performed using Pd(dppf)Cl2 as the catalyst, at temperatures between 65 and 100 °C and in the presence of water and oxygen. This transformation generates 2-arylpyridines in modest to good yields (5%-89%).

Post-Roe emergency medicine: Policy, clinical, training, and individual implications for emergency clinicians.

In June 2022, the United States Supreme Court decision Dobbs v. Jackson Women's Health Organization overturned Roe v. Wade, removing almost 50 years of precedent and enabling the imposition of a wide range of state-level restrictions on abortion access. Historical data from the United States and internationally demonstrate that the removal of safe abortion options will increase complications and the health risks to pregnant patients. Because the emergency department is a critical access point for reproductive health care, emergency clinicians must be prepared for the policy, clinical, educational, and legal implications of this change. The goal of this paper, therefore, is to describe the impact of the reversal of Roe v. Wade on health equity and reproductive justice, the provision of emergency care education and training, and the specific legal and reproductive consequences for emergency clinicians. Finally, we conclude with specific recommended policy and advocacy responses for emergency medicine clinicians.

WOMen profEssioNal developmenT oUtcome Metrics in Academic Emergency Medicine: Results from the WOMENTUM Modified Delphi Study.

INTRODUCTION: To address persistent gender inequities in academic medicine, women professional development groups (PDG) have been developed to support the advancement of women in medicine. While these programs have shown promising outcomes, long-term evaluative metrics do not currently exist. The objective of this study was to establish metrics to assess women's PDGs. METHODS: This was a modified Delphi study that included an expert panel of current and past emergency department (ED) chairs and Academy for Women in Academic Emergency Medicine (AWAEM) presidents. The panel completed three iterative surveys to develop and rank metrics to assess women PDGs. Metrics established by the expert panel were also distributed for member-checking to women EM faculty. RESULTS: The expert panel ranked 11 metrics with high to moderate consensus ranking with three metrics receiving greater than 90% consensus: gender equity strategy and plan; recruitment; and compensation. Members ranked 12 metrics with high consensus with three metrics receiving greater than 90% consensus: gender equity strategy and plan; compensation; and gender equity in promotion rates among faculty. Participants emphasized that departments should be responsible for leading gender equity efforts with PDGs providing a supportive role. CONCLUSION: In this study, we identified metrics that can be used to assess academic EDs' gender equity initiatives and the advisory efforts of a departmental women's PDG. These metrics can be tailored to individual departmental/institutional needs, as well as to a PDG's mission. Importantly, PDGs can use metrics to develop and assess programming, acknowledging that many metrics are the responsibility of the department rather than the PDG.

The Toxicology Investigators Consortium Case Registry-the 2021 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

Reddit discussions about buprenorphine associated precipitated withdrawal in the era of fentanyl.

BACKGROUND: Induction of buprenorphine, an evidence-based treatment for opioid use disorder (OUD), has been reported to be difficult for people with heavy use of fentanyl, the most prevalent opioid in many areas of the country. In this population, precipitated opioid withdrawal (POW) may occur even after individuals have completed a period of opioid abstinence prior to induction. Our objective was to study potential associations between fentanyl, buprenorphine induction, and POW, using social media data. METHODS: This is a mixed methods study of data from seven opioid-related forums (subreddits) on Reddit. We retrieved publicly available data from the subreddits via an application programming interface, and applied natural language processing to identify subsets of posts relevant to buprenorphine induction, POW, and fentanyl and analogs (F&A). We computed mention frequencies for keywords/phrases of interest specified by our medical toxicology experts. We further conducted manual, qualitative, and thematic analyses of automatically identified posts to characterize the information presented. Results: In 267,136 retrieved posts, substantial increases in mentions of F&A (3 in 2013 to 3870 in 2020) and POW (2 in 2012 to 332 in 2020) were observed. F&A mentions from 2013 to 2021 were strongly correlated with mentions of POW (Spearman's ρ: 0.882; p = .0016), and mentions of the Bernese method (BM), a microdosing induction strategy (Spearman's ρ: 0.917; p = .0005). Manual review of 384 POW- and 106 BM-mentioning posts revealed that common discussion themes included "specific triggers of POW" (55.1%), "buprenorphine dosing strategies" (38.2%) and "experiences of OUD" (36.1%). Many reported experiencing POW despite prolonged opioid abstinence periods, and recommended induction via microdosing, including specifically via the BM. CONCLUSIONS: Reddit subscribers often associate POW with F&A use and describe self-managed buprenorphine induction strategies involving microdosing to avoid POW. Further objective studies in patients with fentanyl use and OUD initiating buprenorphine are needed to corroborate these findings.HIGHLIGHTSIncrease in mentions of precipitated opioid withdrawal (POW) on Reddit from 2012 to 2021 was associated with the increase in fentanyl and analog mentions.Experiences of precipitated opioid withdrawal (POW) were described by individuals despite reporting prolonged periods of abstinence compared to standard buprenorphine induction protocols.People with Opioid Use Disorder (OUD) on Reddit are using and recommending microdosing strategies with buprenorphine to avoid POW.People who used fentanyl report experiencing POW following statistically longer periods of abstinence than people who use heroin.