Mesh expansion as the cause of bulging after abdominal wall hernia repair

__Background__ Recurrence is the most important complication of abdominal wall reconstruction. It is pos

Modified classification of Gram-stained vaginal smears to predict spontaneous preterm birth : a prospective cohort study

In a prospective cohort study, we assessed the predictive value of a modified vaginal smear scoring method to identify risk for spontaneous preterm birth

Azapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells

The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based probes that are capped with a cysteine-reactive electrophile for covalent modification of the active site of Mpro. This design led to the most potent ABP for Mpro and one of the most potent inhibitors reported thus far. We demonstrate that this ABP can be used to visualize Mpro activity and target engagement by drugs in infected cells

Novel Aza Peptide Inhibitors and Active-Site Probes of Papain-Family Cysteine Proteases

Recent characterization of multiple classes of functionalized azapeptides as effective covalent inhibitors of cysteine proteases prompted us to investigate O-acyl hydroxamates and their azapeptide analogues for use as activity-based probes (ABPs). We report here a new class of azaglycine-containing O-acylhydroxamates that form stable covalent adducts with target proteases. This allows them to be used as ABPs for papain family cysteine proteases. A second class of related analogues containing a novel O-acyl hydroxyurea warhead was found to function as covalent inhibitors of papain-like proteases. These inhibitors can be easily synthesized on solid support, which allows rapid optimization of compounds with improved selectivity and potency for a given target enzyme. We present here one such optimized inhibitor that showed selective inhibition of falcipain 1, a protease of the malaria-causing parasite, Plasmodium falciparum

Microflora of the penile skin-lined neovagina of transsexual women

<p>Abstract</p> <p>Background</p> <p>The microflora of the penile skin-lined neovagina in male-to-female transsexuals is a recently created microbial niche which thus far has been characterized only to a very limited extent. Yet the knowledge of this microflora can be considered as essential to the follow-up of transsexual women. The primary objective of this study was to map the neo-vaginal microflora in a group of 50 transsexual women for whom a neovagina was constructed by means of the inverted penile skin flap technique. Secondary objectives were to describe possible correlations of this microflora with multiple patients' characteristics, such as sexual orientation, the incidence of vaginal irritation and malodorous vaginal discharge.</p> <p>Results</p> <p>Based on Gram stain the majority of smears revealed a mixed microflora that had some similarity with bacterial vaginosis (BV) microflora and that contained various amounts of cocci, polymorphous Gram-negative and Gram-positive rods, often with fusiform and comma-shaped rods, and sometimes even with spirochetes. <it>Candida </it>cells were not seen in any of the smears.</p> <p>On average 8.6 species were cultured per woman. The species most often found were: <it>Staphylococcus epidermidis</it>, <it>Streptococcus anginosus </it>group spp., <it>Enterococcus faecalis, Corynebacterium </it>sp., <it>Mobiluncus curtisii </it>and <it>Bacteroides ureolyticus</it>. Lactobacilli were found in only one of 30 women</p> <p>There was no correlation between dilatation habits, having coitus, rinsing habits and malodorous vaginal discharge on the one hand and the presence of a particular species on the other. There was however a highly significant correlation between the presence of <it>E. faecalis </it>on the one hand and sexual orientation and coitus on the other (p = 0.003 and p = 0.027 respectively).</p> <p>Respectively 82%, 58% and 30% of the samples showed an amplicon after amplification with <it>M. curtisii</it>, <it>Atopobium vaginae </it>and <it>Gardnerella vaginalis </it>primer sets.</p> <p>Conclusion</p> <p>Our study is the first to describe the microflora of the penile skin-lined neovagina of transsexual women. It reveals a mixed microflora of aerobe and anaerobe species usually found either on the skin, in the intestinal microflora or in a BV microflora.</p