Adapting psychotherapy in collaborative care for treating opioid use disorder and co-occurring psychiatric conditions in primary care.

INTRODUCTION: Opioid use disorder (OUD) and psychiatric conditions commonly co-occur yet are infrequently treated with evidence-based therapeutic approaches, resulting in poor outcomes. These conditions, separately, present challenges to treatment initiation, retention, and success. These challenges are compounded when individuals have OUD and psychiatric conditions. METHOD: Recognizing the complex needs of these individuals, gaps in care, and the potential for primary care to bridge these gaps, we developed a psychotherapy program that integrates brief, evidence-based psychotherapies for substance use, depression, and anxiety, building on traditional elements of the Collaborative Care Model (CoCM). In this article, we describe this psychotherapy program in a primary care setting as part of a compendium of collaborative services. RESULTS: Patients receive up to 12 sessions of evidence-based psychotherapy and case management based on a structured treatment manual that guides treatment via Motivational Enhancement; Cognitive Behavioral Therapies for depression, anxiety, and/or substance use disorder; and/or Behavioral Activation components. DISCUSSION: Novel, integrated treatments are needed to advance service delivery for individuals with OUD and psychiatric conditions and these programs must be rigorously evaluated. We describe our team's efforts to test our psychotherapy program in a large primary care network as part of an ongoing three-arm randomized controlled trial. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Virtual Screening Approach to Identifying a Novel and Tractable Series of Pseudomonas aeruginosa Elastase Inhibitors.

Novel therapies are required to treat chronic bacterial infections in cystic fibrosis (CF) sufferers. The most common pathogen responsible for these infections is Pseudomonas aeruginosa, which persists within the lungs of CF sufferers despite intensive antibiotic treatment. P. aeruginosa elastase (also known as LasB or pseudolysin) is a key virulence determinant that contributes to the pathogenesis and persistence of P. aeruginosa infections in CF patients. The crucial role of LasB in pseudomonal virulence makes it a good target for the development of an adjuvant drug for CF treatment. Herein we discuss the discovery of a new series of LasB inhibitors by virtual screening and computer assisted drug design (CADD) and their optimization leading to compounds 29 and 39 (K i = 0.16 µM and 0.12 µM, respectively).

Design of Selective Benzoxazepin PI3Kδ Inhibitors Through Control of Dihedral Angles.

A novel selective benzoxazepin inhibitor of PI3Kδ has been discovered. Beginning from compound 3, an αPI3K inhibitor, we utilized structure-based drug design and computational analysis of dihedral torsion angles to optimize for PI3Kδ isoform potency and isoform selectivity. Further medicinal chemistry optimization of the series led to the identification of 24, a highly potent and selective inhibitor of PI3Kδ.

Physiological factors influencing toughness in cooked Saddletail snapper (Lutjanus malabaricus).

UNLABELLED: Saddletail snapper (Lutjanus malabaricus) is a commercially significant tropical species in Australia and has been the subject of consumer complaints of extreme toughness in cooked fillets. Textural and biochemical analyses including collagen and hydroxylysyl pyridinoline (PYD) cross-links concentrations were conducted on 101 commercially harvested Saddletail snapper to identify causes of toughness. Fish age was found to account for 75.6% of observed variation in cooked muscle texture (work done) of Saddletail snapper. A significant linear relationship (P < 0.001) between PYD content and cooked muscle texture was also identified accounting for 50.3% of observed variation. The concentration ratio of PYD to total collagen (TC) ranged from 0.04 to 0.38 mol PYD per mol of TC. Fish size was also found to be a poor indicator of fish age and therefore a poor indicator of the potential risk of toughness of the cooked muscle. PRACTICAL APPLICATION: Some tropical fish species of commercial significance can grow reasonably old without growing into particularly large fish. These fish can have a cooked meat texture that is very firm and not dissimilar to that of cooked chicken meat. These species should be marketed as such and not targeted toward existing markets and consumers more familiar with fish species with softer meat texture.

Synthesis and properties of macrolones characterized by two ether bonds in the linker.

In this paper synthesis of macrolones 1-18 starting from azithromycin is reported. Two key steps in the construction of the linker between macrolide and quinolone moiety, are formation of central ether bond by alkylation of unactivated OH group, and formation of terminal C-C bond at 6-position of the quinolone unit. Due to the difficulty in formation of these two bonds the study of alternative synthetic methodologies and optimization of the conditions for the selected routes was required. Formation of C-4''-O-ether bond was completed by modified Michael addition, whereas O-alkylation via diazonium cation proved to be the most effective in formation of the central allylic or propargylic ether bond. Comparison of Heck and Sonogashira reaction revealed the former as preferred route to the C-C bond formation at C(6) position of the quinolone unit. Most of the target compounds exhibited highly favorable antibacterial activity against common respiratory pathogens, without significant cytotoxicity profile when tested in vitro on eukaryotic cell lines.

Localized periodontitis as a long-term effect of oral piercing: a case report.

Recent years have seen a dramatic increase in the number of published articles on short-term complications of oral piercing, possibly reflecting an increase in the popularity of this practice. Long-term effects of oral piercing, however, have had minimal documentation. This case report of a 28-year-old woman with piercing of the tongue and lower lip demonstrated localized severe periodontitis as a destructive long-term outcome related to oral piercing. The patient reported that she had worn 2 tongue rings and a mandibular labrette (lip piercing) in the form of a bar for 12 years. Plaque and calculus accumulation, severe inflammation, tooth mobility, severe horizontal radiographic bone loss, and deep pocketing were observed in teeth affected by the jewelry.

Discovery and optimisation of potent, selective, ethanolamine inhibitors of bacterial phenylalanyl tRNA synthetase.

High throughput screening of Staphylococcus aureus phenylalanyl tRNA synthetase (FRS) identified ethanolamine 1 as a sub-micromolar hit. Optimisation studies led to the enantiospecific lead 64, a single-figure nanomolar inhibitor. The inhibitor series shows selectivity with respect to the mammalian enzyme and the potential for broad spectrum bacterial FRS inhibition.

Definition of the heterocyclic pharmacophore of bacterial methionyl tRNA synthetase inhibitors: potent antibacterially active non-quinolone analogues.

Potent inhibitors of bacterial methionyl tRNA synthetase (MRS) have previously been reported. Through SAR of the quinolone moiety, the right hand side pharmacophore for MRS inhibition has now been defined as an NH-C-NH functionality in the context of a bicyclic heteroaromatic system. Potent antibacterial fused-pyrimidone and fused-imidazole analogues have been obtained and enantioselective activity demonstrated. Compound 46 demonstrated very good antibacterial activity against panels of antibiotic-resistant staphylococci and enterococci.

Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207.

Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.

Optimisation of aryl substitution leading to potent methionyl tRNA synthetase inhibitors with excellent gram-positive antibacterial activity.

Optimisation of the left-hand-side aryl moiety of a file compound screening hit against Staphylococcus aureus methionyl tRNA synthetase led to the identification of a series of potent nanomolar inhibitors. The best compounds showed excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics.

Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens.

Potent nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase have been derived from a file compound high throughput screening hit. Optimized compounds show excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics. Compound 11 demonstrated in vivo efficacy in an S. aureus rat abscess infection model.