"One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices and outcomes for gestational surrogate patients

In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs and sperm provided by the intended father went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making. This paper focuses on multipleembryo transfers in the context of U.S. surrogacy arrangements. Offering an original analysis of data obtained from the U.S. national assisted reproduction registry, it examines single- and multiple-embryo transfer trends over an eleven-year period (2003 to 2014). Findings reveal that recommended guidelines were followed in less than 42% of cases in 2014. The paper argues that ensuring equitable medical treatment for all recipients of IVF requires the adoption of treatment guidelines tailored to, and offering protections for, specific patient groups, and that, once in place, guidelines must be robustly implemente

Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum

BACKGROUND Malaria invasion of red blood cells involves multiple parasite-specific targets that are easily accessible to inhibitory compounds, making it an attractive target for antimalarial development. However, no current antimalarial agents act against host cell invasion. RESULTS Here, we demonstrate that the clinically used macrolide antibiotic azithromycin, which is known to kill human malaria asexual blood-stage parasites by blocking protein synthesis in their apicoplast, is also a rapid inhibitor of red blood cell invasion in human (Plasmodium falciparum) and rodent (P. berghei) malarias. Multiple lines of evidence demonstrate that the action of azithromycin in inhibiting parasite invasion of red blood cells is independent of its inhibition of protein synthesis in the parasite apicoplast, opening up a new strategy to develop a single drug with multiple parasite targets. We identified derivatives of azithromycin and erythromycin that are better invasion inhibitors than parent compounds, offering promise for development of this novel antimalarial strategy. CONCLUSIONS Safe and effective macrolide antibiotics with dual modalities could be developed to combat malaria and reduce the parasite’s options for resistance.Danny W Wilson, Christopher D Goodman, Brad E Sleebs, Greta E Weiss, Nienke WM de Jong, Fiona Angrisano, Christine Langer, Jake Baum, Brendan S Crabb, Paul R Gilson, Geoffrey I McFadden, and James G Beeso

Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp.

BACKGROUND: Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. METHODS: Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. RESULTS: Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MIC’s for equisetin were 8 μg mL(−1) against Bacillus subtilis, 16 μg mL(−1) against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). CONCLUSIONS: O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads