Search

Management of complex regional pain syndrome after lower extremity trauma is difficult. The use of a continuous epidural blockade enhances the results of lower extremity peripheral nerve surgery. This article presents our experience using this approach for the management of these patients. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an N -alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular N -alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug market rapidly. In response to the large number of SCRAs that have been detected, pharmacological evaluation of this NPS class has become increasingly common. Adamantane-derived SCRAs have consistently appeared throughout the market since 2011, and as such, a systematic set of these derivatives was synthesized and pharmacologically evaluated. Deuterated and fluorinated adamantane derivatives were prepared to evaluate typical hydrogen bioisosteres, as well as evaluation of the newly detected AFUBIATA.

The generation and Giese-type reaction of alanyl radicals under metal-free reaction conditions is described. The procedure is operationally simple, occurring at ambient temperature in an open reaction vessel, and requiring short reaction times (≤5 min). The reaction occurs without epimerization and provides ready access to non-proteinogenic amino acids and peptides. Importantly, the process is tolerant of light absorbing groups including commonly used fluorescent tags.

Over 200 synthetic cannabinoid receptor agonists (SCRAs) have been identified as new psychoactive substances. Effective monitoring and characterization of SCRAs are hindered by the rapid pace of structural evolution. Ahead of possible appearance on the illicit drug market, new SCRAs were synthesized to complete a systematic library of cumyl-indole- ( e.g. , CUMYL-CPrMICA, CUMYL-CPMICA) and cumyl-indazole-carboxamides ( e.g. , CUMYL-CPrMINACA, CUMYL-CPMINACA), encompassing butyl, pentyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, and cyclohexylmethyl tails. Comprehensive pharmacological characterization was performed with three assay formats, monitoring the recruitment of either wild-type or C-terminally truncated (βarr2d366) β-arrestin2 to the activated cannabinoid 1 receptor (CB 1 ) or monitoring G βγ -mediated membrane hyperpolarization. Altered compound characterization was observed when comparing derived potency (EC 50 ) and efficacy ( E max ) values from both assays monitoring the same or a different signaling event, whereas ranges and ranking orders were similar. Structure-activity relationships (SAR) were assessed in threefold, resulting in the identification of the pendant tail as a critical pharmacophore, with the optimal chain length for CB 1 activation approximating an n- pentyl ( e.g. , cyclopentylmethyl or cyclohexylmethyl tail). The activity of the SCRAs encompassing cyclic tails decreased with decreasing number of carbons forming the cyclic moiety, with CUMYL-CPrMICA showing the least CB 1 activity in all assay formats. The SARs were rationalized via molecular docking, demonstrating the importance of the optimal steric contribution of the hydrophobic tail. While SAR conclusions remained largely unchanged, the differential compound characterization by both similar and different assay designs emphasizes the importance of detailing specific assay characteristics to allow adequate interpretation of potencies and efficacies.

Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS). They commonly comprise N -alkylated indole, indazole, or 7-azaindole scaffolds with amide-linked pendant amino acid groups. To explore the contribution of the amino acid side chain to the cannabinoid pharmacology of SCRA NPS, a systematic library of side chain-modified SCRAs was prepared based on the recent detections of amino acid derivatives 17 (5F-AB-PINACA), 18 (5F-ADB-PINACA), 15 (PX-1), 19 (PX-2), and 20 (NNL-1). In vitro binding affinities and functional activities at cannabinoid type 1 and 2 receptors (CB 1 and CB 2 , respectively) were determined for all the library members using radioligand competition experiments and a fluorescence-based membrane potential assay. Binding affinities and functional activities varied widely across compounds ( K i = 0.32 to >10 000 nM, EC 50 = 0.24-1259 nM), with several clear structure-activity relationships (SARs) emerging. Affinity and potency at CB 1 changed as a function of the heterocyclic core (indazole > indole > 7-azaindole) and the pendant amino acid side chain ( tert -butyl > iso -propyl > iso -butyl > benzyl > ethyl > methyl > hydrogen). Ensemble docking at CB 1 revealed a clear steric basis for observed SAR trends. Interestingly, although 15 (PX-1) and 19 (PX-2) have been detected in recreational drug markets, they failed to induce centrally CB 1 -mediated effects (e.g., hypothermia) in mice using radiobiotelemetry. Together, these data provide insights regarding structural contributions to the cannabimimetic profiles of 17 (5F-AB-PINACA), 18 (5F-ADB-PINACA), 15 (PX-1), 19 (PX-2), 20 (NNL-1), and other SCRA NPS.

Introduction: Tobacco use remains pervasive amongst veterans. Unfortunately, the negative impact on postoperative outcomes may preclude surgeons from offering operative intervention to veterans who smoke. As such, a major health event may provide added incentive to quit. We sought to describe the role of acute illness and interventional specialist involvement in Veterans Affairs Smoking Cessation Program referrals compared to primary care wellness initiatives., Methods: We retrospectively reviewed consultations to the pharmacy-led Smoking Cessation Program (SCP) at the Middleton Memorial VA Hospital from 2017 to 2019. Consultations placed during the last three months were categorized based on the source of referral: primary care, acute care, and interventional specialties. Descriptive statistics were used to assess rates of veteran engagement based on referral source. Consultation completion was used as a proxy for veteran engagement., Results: A total of 2993 new SCP consultations were placed during the study period. Overall, veteran engagement rose from 43% in 2017 to 53% in 2019. In recent months, there were 282 SCP referrals. While only 19 (7%) of these referrals were placed by interventional specialties - primarily cardiology and thoracic surgery - the rate of veteran engagement was 63%. The majority of referrals (65%) were placed by primary care providers with an engagement rate of 68%. In contrast, only 42% of consultations placed in the context of an acute illness were completed., Conclusions: In our study, primary care directed smoking cessation referrals were most prevalent and resulted in the highest completion rates. The presence of an acute illness in isolation failed to impact program success. However, while surgeon-initiated referrals were meager in number, the engagement rate approached that of primary care. This finding suggests that surgeons play a powerful role in influencing patient behavior that may be harnessed to augment success of existing smoking cessation programs., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. J. Maloney reports funding from Ethicon and Medtronic, outside the submitted work., (© 2021 Maloney J. C. et al.)

Homologous and heterologous skin test reactions in sensitized guinea pigs to antigens from 11 species of mycobacteria were fitted by a linear model that permitted the ranking of each species on the basis of cross reactivity. When the same species were ranked on the basis of in vitro transformation of sensitive lymphocytes in response to homologous and heterologous antigen preparations, a different ranking order was observed. Reasons for the lack of strict correlation between skin tests and in vitro lymphocyte transformations are discussed.

The assayed potency of an adsorbed tetanus toxoid C(2), relative to the international standard for tetanus toxoid (adsorbed), varied significantly with the use of different strains of mice. The unitage was highest with NIH mice, and it was not significantly different from that with CFW mice. With CDF(1) and BALB/c mice, however, the assayed potency was significantly lower than with NIH mice. C3H mice failed to respond to the dose range of the toxoids employed with the other four strains. The significance of the influence of the mouse strain on the designation of a prescribed unit requirement for tetanus toxoid, adsorbed, relative to human efficacy is discussed.

Haemagglutination (HA) has been used frequently for the titration of tetanus antitoxin but published results have varied in relation to the "unitage" determined by the mouse toxin-neutralization test (TN). This report gives the results of the titration of a group of sera by haemagglutination and compares them with the results obtained by toxin neutralization. Although there was marked variation between HA and TN titres of individual sera, results indicated that haemagglutination is a useful procedure for the over-all evaluation of the antitoxin responses to tetanus toxoids in field studies.

Quantitation of soluble residual host protein in chicken embryo-derived vaccines was performed rapidly, economically, and accurately by radial immunodiffusion.