Photocatalytic Thiol-Yne Reactions of Alkynyl Sulfides.

Thiol-yne reactions typically employ thiols and terminal alkynes as the reaction partners. The thiol-yne reaction of alkynyl sulfides and thiols is possible when employing a nonmetal photocatalyst eosin Y, green LED irradiation, under an air atmosphere. Alkynyl sulfides were transformed in good overall yields (58-90% total yields, 11 examples) favoring the cis isomer. No addition to the α-position of the alkynyl sulfide is observed, and regioselectivity is believed to be controlled through the stabilization of radical intermediates by the adjacent sulfur atom. Furthermore, control experiments with "all-carbon" internal alkynes demonstrate that alkynyl sulfides possess improved reactivity and regioselectivity profiles during thiol-yne processes.

A Research Agenda to Inform Cannabis Regulation: How Science Can Shape Policy.

In the United States, changes to cannabis policy have outpaced scientific knowledge about cannabis, its effects, and the impacts of different policy approaches. Research barriers stem from key federal policies, including strict drug scheduling of cannabis, which comprehensively hinder the ability to conduct cannabis research, affecting state markets, evidence-based regulation, and scientific gains that could more effectively shape policy moving forward. The Cannabis Regulators Association (CANNRA) is a nonpartisan nonprofit organization that convenes and supports government agencies to facilitate information exchange and learning from existing cannabis regulations across US states and territories and other governmental jurisdictions. This commentary outlines a research agenda that, if implemented, would address critical gaps in the science that cannabis regulators have identified in terms of knowledge regarding: (1) medicinal use of cannabis; (2) cannabis product safety; (3) cannabis consumer behaviors; (4) policies to promote equity and reduce disparities, both in the industry and more broadly in communities affected by the past criminalization of cannabis; (5) policies to prevent youth consumption and promote public health and safety; and (6) policies to reduce the illicit market and associated harms. The research agenda outlined here is the result of both formal discussions through CANNRA-wide meetings and informal discussions cannabis regulators have had as part of CANNRA committees. This research agenda is not all encompassing but rather highlights areas of research that have vital importance for cannabis regulation and policy implementation. Although many organizations weigh in on research needs related to cannabis, cannabis regulators (ie, the individuals implementing policies legalizing cannabis in states and territories) have generally not had a voice at the table advocating for specific research to be conducted. Their perspective representing the government agencies closest to the ground in terms of experiencing the impacts of current cannabis policy is essential to furthering quality, practical research that can advance informed and effective policy.

Heteroleptic Copper(I)-Based Complexes Incorporating BINAP and π-Extended Diimines: Synthesis, Catalysis and Biological Applications.

A series of copper-based photocatalysts of the type Cu(NN)(BINAP)BF4 were synthesized bearing π-extended diimine ligands. Their behavior in several photocatalytic processes were evaluated and revealed acceptable levels of activity in an SET process, but negligible activity in PCET or ET processes. Suitable activity in ET processes could be restored through modification of the ligand. The BINAP-derived complexes were then evaluated for activity against triple-negative breast cancer cell lines. Controls indicated that copper complexes, and not their ligands, were responsible for activity. Encouraging activity was displayed by a homoleptic complex Cu(dppz)2BF4.

Computational Insight into Cu-Catalyzed Csp-S Coupling to Form a Macrocyclic Alkynyl Sulfide.

Copper-catalyzed Csp-S cross-coupling is known to form rare macrocyclic alkynyl sulfides. Computational studies now suggest a mechanism for the reaction pathway. Upon formation of Cu-S species, subsequent α-addition/elimination at the ethynylic carbon affords the desired macrocycle.

Anesthesia and Perioperative Considerations for Patients With Myasthenia Gravis.

Patients with neuromuscular diseases such as myasthenia gravis can present as complicated anesthetic cases. This article reviews anesthetic considerations for optimal perioperative care of patients with myasthenia gravis. The pathophysiology of myasthenia gravis, cholinergic and myasthenic crises, and perioperative management are discussed; this includes the pharmacology of acetylcholinesterase inhibitors vs sugammadex, extubation criteria, pain management, and risk factors for postoperative myasthenic crisis. Anesthesia recommendations include reversal of nondepolarizing neuromuscular blockade agents with sugammadex, obtaining sufficient spontaneous breathing with absolutely no residual curarization before extubation, limited use of opioids and sedatives, avoidance of routine admission to the intensive care unit, and consideration of peripheral nerve blocks for adjunct pain control.

Synthesis and Diversification of Macrocyclic Alkynediyl Sulfide Peptides.

The synthesis of rare macrocyclic alkynediyl sulfides by a Cu-catalyzed Csp -S cross-coupling is presented. The catalytic protocol (Cu(MeCN)4 PF6 /dtbbpy) promotes macrocyclization of peptides, dipeptides and tripeptides at ambient temperature (14 examples, 23→73 % yields) via thiols and bromoalkynes, and is chemoselective with regards to terminal alkynes. Importantly, the underexplored alkynediyl sulfide functionality incorporates a rigidifying structural element and opens new opportunities for diversification of macrocyclic frameworks through S oxidation, halide addition and azide-alkyne cycloaddition chemistries to integrate sulfones, halides or valuable fluorophores (7 examples, 37→92 % yields).

General Cu-Catalyzed Csp-S Coupling.

Copper-catalyzed cross-coupling of thiols and bromoalkynes affords a mild, rapid, and selective Csp-S coupling with broad scope, enabling the use of aryl-, alkyl-, and silyl-substituted alkynyl coupling partners (38 total examples, 50-99% yields). Importantly, the method enables the preparation of difficult-to-access bis-heteroatom-functionalized (S,S-, S,P-, and S,N-) alkynes.

A synthetic guide to alkynyl sulfides.

The relative stability and predictable reactivity of alkynyl sulfides make them ideal synthons for the development of new transformations. Classic methods for forming alkynyl sulfides relied on dehydrohalogenation approaches. However more recent methods have focused on employing umpolung strategies, as well as nucleophilic and electrophilic thiol alkynylation. In addition, the recent syntheses of Csp-S bonds have trended towards exploiting catalysis and expanding the reaction scope of the methods. A survey of existing methods to form alkynyl sulfides is presented as well as an evaluation with regards to the scope of each method, to provide the reader with an overview of advantages and limitations of current technology.

Biocatalytic synthesis of planar chiral macrocycles.

Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.

Comparing Forced-Air to Resistive-Polymer Warming for Perioperative Temperature Management: A Retrospective Study.

PURPOSE: Compare perioperative temperature management between forced-air warming (FAW) and resistive-polymer heating blankets (RHBs). DESIGN: A retrospective, quasi-experimental study. METHODS: Retrospective data analysis of nonspine orthopedic cases (N = 426) over a one-year period including FAW (n = 119) and RHBs (n = 307). FINDINGS: FAW was associated with a significantly higher final intraoperative temperature (P = .001, d = 0.46) than the RHB. The incidence of hypothermia was not found to be significantly different at the end (P = .102) or anytime throughout surgery (P = .270). Of all patients who started hypothermic, the FAW group had a lower incidence of hypothermia at the end of surgery (P = .023). CONCLUSIONS: FAW was associated with higher final temperatures and a greater number of normothermic patients than RHBs. However, no causal relationship between a warming device and hypothermia incidence should be assumed.

Prevention and Treatment of Laryngospasm in the Pediatric Patient: A Literature Review.

Laryngospasm is an exaggeration of a protective reflex that prevents aspiration of foreign objects into the lower airway (eg, during swallowing). This results in complete or partial closure of the glottis, and impedance or total obstruction of airflow to the trachea and lungs. Often, the resulting hypoxia will by itself break a laryngospasm; however, if the spasm continues without relief, it can lead to pulmonary edema, cardiac dysrhythmias, cardiac arrest, and ultimately death. This evidence-based literature review explores the pathophysiology of laryngospasm and covers mechanical and pharmacologic prevention and treatment modalities in pediatric patients.

Risk Factors for Perioperative Hypothermia: A Literature Review.

PURPOSE: The purpose of this article was to review the literature to identify risk factors for the development of unplanned perioperative hypothermia and to evaluate the strength of the evidence for each risk factor. DESIGN: Comprehensive literature review METHODS: An evidence rating scale was used to evaluate the strength and quality of the research gathered. FINDINGS: At this time, only anecdotal evidence is available to guide our efforts in the maintenance of perioperative normothermia. There is currently no strong evidence to implicate risk factors that do or do not cause a patient to develop unplanned perioperative hypothermia. CONCLUSIONS: It is crucial to prevention that health care providers are able to identify risk factors and implement interventions. However, vigilance in the perioperative period can only enhance patient safety when we know what to look for. More research is needed to identify risk factors of unplanned perioperative hypothermia and effectively maintain normothermia throughout the perioperative period.

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow.

A copper-based photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their anhydrides. The protocol was also amendable and optimized under continuous flow conditions.

Heteroleptic Copper(I)-Based Complexes for Photocatalysis: Combinatorial Assembly, Discovery, and Optimization.

A library of 50 copper-based complexes derived from bisphosphines and diamines was prepared and evaluated in three mechanistically distinct photocatalytic reactions. In all cases, a copper-based catalyst was identified to afford high yields, where new heteroleptic complexes derived from the bisphosphine BINAP displayed high efficiency across all reaction types. Importantly, the evaluation of the library of copper complexes revealed that even when photophysical data is available, it is not always possible to predict which catalyst structure will be efficient or inefficient in a given process, emphasizing the advantages for catalyst structures with high modularity and structural variability.

Nitrous Oxide for the Management of Labor Analgesia.

This article reviews nitrous oxide and explores current practice standards for use of nitrous oxide in managing labor analgesia. Inhaled nitrous oxide is used in the labor process for analgesia as well as for anxiolysis in many countries but is rarely offered in the United States. Because of its minimal invasiveness, highsafety index, effectiveness, and relatively low cost, it is reemerging as a consideration for use during labor and is worthy of further research.

Photochemical Dual-Catalytic Synthesis of Alkynyl Sulfides.

A photochemical dual-catalytic cross-coupling to form alkynyl sulfides via C(sp)-S bond formation is described. The cross-coupling of thiols and bromoalkynes is promoted by a soluble organic carbazole-based photocatalyst using continuous flow techniques. Synthesis of alkynyl sulfides bearing a wide range of electronically and sterically diverse aromatic alkynes and thiols can be achieved in good to excellent yields (50-96 %). The simple continuous flow setup also allows for short reaction times (30 min) and high reproducibility on gram scale. In addition, we report the first application of photoredox/nickel dual catalysis towards macrocyclization, as well as the first example of the incorporation of an alkynyl sulfide functional group into a macrocyclic scaffold.

Phase Separation Macrocyclization in a Complex Pharmaceutical Setting: Application toward the Synthesis of Vaniprevir.

A phase separation/continuous flow strategy employing an oxidative Glaser-Hay coupling of alkynes has been applied toward the synthesis of the macrocyclic core of complex pharmaceutical vaniprevir. The phase separation/continuous flow strategy afforded similar yields at 100-500 times the concentration and at shorter reaction times than common slow addition/high dilution techniques. In addition, dendritic PEG cosolvents were employed in the phase separation strategy for the first time and shown to allow productive macrocyclization at concentrations up to 200 mM.

Total Synthesis of Neomarchantin A: Key Bond Constructions Performed Using Continuous Flow Methods.

A synthesis of neomarchantin A has been achieved wherein key bond constructions involving C-O or C-C bond formations were augmented via continuous flow techniques. Of note, the synthesis of neomarchantin A represents the first demonstration of catalytic macrocyclic olefin metathesis as a key step for the synthesis of a macrocyclic bisbibenzyl natural product.

Foreign-Educated Graduate Nursing Students and Plagiarism.

BACKGROUND: Plagiarism is a concern related to students educated in countries other than the United States, where English is not the first language spoken. The authors' experience with plagiarism by a foreign-educated nursing student prompted an investigation into this topic. METHOD: This article focuses on the occurrence of unintentional plagiarism, a common focus with foreign-educated students, addressing linguistic, as well as cultural, viewpoints. RESULTS: The findings from the literature on plagiarism among foreign-educated students are elicited and the article discusses strategies to help foreign-educated students learn about plagiarism and how to properly cite and reference sources. CONCLUSION: A variety of proactive strategies exist that can be used by both faculty and students to mitigate the occurrence of plagiarism by foreign-educated nursing students in higher education, starting with a clearer understanding of some of the antecedents to the problem of plagiarism. [J Nurs Educ. 2017;56(4):211-214.].

Social Media in Nurse Anesthesia: A Model of a Reproducible Educational Podcast.

Social media and specifically podcasting are available to the field of nurse anesthesia as potential educational tools. This article outlines key concepts in social media, including free open access medical education and literature supporting the use of podcasting in higher, medical, and nursing education. The authors provide an educational model useful for developing social media tools and a logic model for producing an educational podcast. These tools were used in the production of the authors' educational anesthesia podcast, and key steps are outlined. The goal of this article is to provide an overview of social media and relevant resources so that other educational podcasts may be developed for the nurse anesthesia community.