Chemo-enzymatic synthesis of bicyclic gamma-lactams using clavaminic acid synthase

Incubation of the γ-lactam analogue of proclavaminic acid, (±)-threo-5-amino-3-hydroxy-2-(1'-aza-2'-oxocyclopentyl) acid, led to production of two bicyclic γ-lactam products

Product-substrate engineering by bacteria: Studies on clavaminate synthase, a trifunctional dioxygenase

Evidence is presented that clavaminate synthase (CS) catalyses three oxidative reactions in the clavulanic acid biosynthetic pathway. The first CS catalysed step (hydroxylation) is separated from the latter two (oxidative cyclisation and desaturation) by the action of a hydrolytic enzyme, proclavaminate amidinohydrolase, which modifies (or 'mutates') the sidechain of the product of the first reaction thereby converting it into a substrate for the second CS catalysed reaction

The Cost and Intensity of Behavioral Interventions to Promote HIV Treatment for Prevention Among HIV-Positive Men Who Have Sex with Men

Recently, behavioral prevention interventions for HIV have been criticized as being ineffective, costly, or inefficient. In this commentary, using HIV-positive men who have sex with men (MSM) as an illustrative high-risk population, we argue that the opposite is true – that behavioral interventions for HIV prevention, if implemented with the populations who need them, are affordable and critical for future prevention efforts. We base this argument on recent evidence showing that 1) adherence to antiretroviral treatment (ART) for prevention purposes is necessary to suppress HIV replication and reduce transmissibility, 2) individuals living with HIV have multiple psychosocial concerns that impact self-care and moderate the potential effectiveness of health behavior interventions, and 3) intensive interventions targeting both concerns together (psychosocial and HIV care) can show clinically significant improvement. We follow by comparing the cost of these types of interventions to the cost of standard clinical treatment for HIV with ART, and demonstrate a cost-savings of potential intensive behavioral interventions for, in this case, HIV-positive MSM who have uncontrolled virus. Keeping this evidence in mind, we conclude that individual intervention must remain a mainstay of HIV prevention for certain critical populations

Advances in HIV Prevention for Serodiscordant Couples

Serodiscordant couples play an important role in maintaining the global HIV epidemic. This review summarizes biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014, including World Health Organization guidelines and best-evidence for couples counseling, couples-based interventions, and the use of antiviral agents for prevention. In the past few years marked advances have been made in HIV prevention for serodiscordant couples and numerous ongoing studies are continuously expanding HIV prevention tools, especially in the area of pre-exposure prophylaxis. Uptake and adherence to antiviral therapy remains a key challenge. Additional research is needed to develop evidence-based interventions for couples, and especially for male-male couples. Randomized trials have demonstrated the prevention benefits of antiretroviral-based approaches among serodiscordant couples; however, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention