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This study reports on the preparation of eight new boron-containing capsaicinoids bearing long aliphatic chains, as an expansion of our previous studies to include tertiary amide derivatives into our substrate scope. Our boron-moiety, a pinacolboronate ester (Bpin) fragment, has been incorporated in two locations: as an aryl substituent of the capsaicinoid produced by the reductive amination of veratraldehyde, or at the terminal end of an aliphatic substituent using an iridium catalyzed hydroboration reaction. We report that most compounds in our series show moderate antimicrobial and cytotoxic activity, surpassing activities noted in our previous study.

Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications.

Objective To assess the effects of delayed vs immediate pushing in second stage of labour with epidural analgesia on delivery outcome, postpartum faecal continence and postpartum anal sphincter and pudendal nerve function. Design Prospective, randomised, controlled trial. Setting Tertiary referral maternity teaching hospital. Population One hundred and seventy nulliparous women randomised at full dilatation to immediate or delayed pushing. Methods A total of 178 nulliparous women, all with continuous epidural analgesia, were randomised at full cervical dilatation, but before the fetal head had reached the pelvic floor, to either immediate pushing or 1 hour delayed pushing. Labour outcome was analysed and all women underwent postpartum assessment of anal sphincter function, including anal manometry. Those women who had a normal delivery underwent neurophysiology studies, while those women who had an instrumental delivery underwent endoanal ultrasound. Main outcome measures Mode of delivery; altered faecal continence. Results Ninety women were randomised to immediate pushing and 88 to delayed pushing. The spontaneous delivery rate was 56% (50/90) in the immediate pushing group and 52% (46/88) in the delayed pushing group. Mean duration of labour for the immediate pushing group was 427 minutes compared with 480 minutes for the delayed pushing group (P = 0.005). Eighty-four percent (76/90) of women in the immediate pushing group received oxytocin to augment labour, 21/76 (28%) in the second stage only. Eighty-one percent (71/88) of women in the delayed pushing group received oxytocin to augment labour, 22/71 (31%) in the second stage only. Fetal outcome did not differ between the two groups. Episiotomy rates were 73% and 69% in the immediate pushing and delayed pushing groups, respectively. 26% (23/90) of the immediate pushing group and 38% (33/88) of the delayed pushing group complained of altered faecal continence after delivery (NS). Manometry, ultrasound and neurophysiology studies did not differ significantly between the two groups. Overall, 55% of women after instrumental delivery had endosonographic evidence of damage to the external anal sphincter, while 36% of women after spontaneous delivery had abnormal neurophysiology studies. Conclusions Rates of instrumental delivery were similar following immediate and delayed pushing, in association with epidural analgesia. Delayed pushing prolonged labour by 1 hour but did not result in significantly higher rates of altered continence or anal sphincter injury, when compared with immediate pushing.

New macromolecules such as dendrimers are increasingly needed to drive breakthroughs in diverse areas, for example, healthcare. Here, the authors report hybrid antimicrobial dendrimers synthesized by functionalizing organometallic dendrimers with quaternary ammonium groups or 2-mercaptobenzothiazole. The functionalization tunes the glass transition temperature and antimicrobial activities of the dendrimers. Electron paramagnetic resonance spectroscopy reveals that the dendrimers form free radicals, which have significant implications for catalysis and biology. In vitro antimicrobial assays indicate that the dendrimers are potent antimicrobial agents with activity against multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium as well as other microorganisms. The functionalization increases the activity, especially in the quaternary ammonium group-functionalized dendrimers. Importantly, the activities are selective because human epidermal keratinocytes cells and BJ fibroblast cells exposed to the dendrimers are viable after 24 h.