Recent achievements in transcatheter closure of ventricular septal defects : a systematic review of literature and a meta-analysis

Background: Ventricular septal defect (VSD) is one of the most common congenital heart defects. Currently, surgery remains the treatment of choice. However, transcatheter techniques for closing of various types of VSDs have become an alternative. Aims: The objective of our study was to present the outcomes of transcatheter closure of various types of VSD based on a systematic review of recent publications. Methods: A systematic review of studies published in English between January 2014 and March 2020 was performed using the PubMed database (MEDLINE) independently by 2 reviewers. Data on success and complication rates were extracted. Studies including fewer than 5 patients and those with acquired VSD were excluded from the analysis. Results: Finally, 44 studies were included for analysis, with a total number of 4050 patients. The pooled estimate of the overall success rate based on the random effects model was 97.96% (95% CI, 97.37–98.56; Q test P 0.99; I 2 = 0%) for permanent VSD. Conclusions: Transcatheter closure of selected VSDs appears to be an effective and safe method of treatment. Recent studies have shown high rates of successful interventions with a low incidence of complications

Covalent host-targeting by thioester domains of Gram-positive pathogens

Gram-positive pathogens are a major concern to global health, with increasing resistance to antimicrobials and the lack of preventative therapeutics. Understanding how these bacteria interact with host cells is vital for the development of novel strategies to combat disease. One of the most crucial steps in infection is adhesion to the host cell. The discovery of complex cell-surface associated proteins, such as pili, has advanced our knowledge of this interaction, however the precise molecular mechanisms underlying this process remain unclear. Structural studies of pili revealed the presence of highly unusual intramolecular covalent bonds between amino acid side chains. These include isopeptide bonds between Lys and Asp/Asn residues, conferring mechanical strength, thermal stability and resistance to proteases [1,2]. In Streptococcus pyogenes pili, the adhesin Spy0125 (or Cpa) interacts with the host cell. It comprises three domains, two of which contain stabilising isopeptide bonds [2,3]. Intriguingly, the third domain contains an extremely rare thioester bond, between a Cys and a Gln residue. A Cys to Ala mutation results in a 75% reduction in adhesion, suggesting that this internal linkage may mediate direct attachment [3]. We have now discovered putative thioester domains (TEDs) in cell-surface proteins of several clinically important pathogens. The only other example of an internal thioester is found in complement proteins, where the reactive bond enables the formation of covalent attachment to pathogens. The presence of these bonds in bacterial proteins suggests the possibility of an as-yet uncharacterised, conserved mechanism of covalent host cell attachment. For a selection of pathogens, we have used mass spectrometry and crystallography to confirm the presence of the covalent link between the Cys and Gln residues within the TEDs. Furthermore, we have identified putative host cell targets of TEDs and confirmed covalent linkages between the TED and the target.</jats:p

An internal thioester in a pathogen surface protein mediates covalent host binding

This work was supported by the MRC, UK grant MR/K001485 for MW, JME, MR, MJB, USL; the BBSRC, UK grant BB/J00453 and the John Innes Foundation for MJB; the Wellcome Trust Institutional Strategic Support Fund 097831/Z/11/B for AMD; Wellcome Trust/JIF award 063597 and Wellcome Trust grants WT079272AIA and 094476/Z/10/Z to CHB for the BSRC Mass Spectrometry and Proteomics Facility; University of St Andrews and School of Biology for SYK; The Carnegie Trust for OKM.To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions.Publisher PDFPeer reviewe

Influence of the Support Composition on the Activity of Cobalt Catalysts Supported on Hydrotalcite-Derived Mg-Al Mixed Oxides in Ammonia Synthesis

Recently, catalysts with hydrotalcites and hydrotalcite-derived compounds have attracted particular interest due to their specific properties, mostly well-developed texture, high thermal stability, and favorable acid&ndash;base properties. In this work, we report the investigation of ammonia synthesis on barium-promoted cobalt catalysts supported on hydrotalcite-derived Mg-Al mixed oxides with different Mg/Al molar ratios. The obtained catalysts were characterized using TGA-MS, nitrogen physisorption, XRPD, TEM, STEM-EDX, H2-TPD, CO2-TPD, and tested in ammonia synthesis (470 &deg;C, 6.3 MPa, H2/N2 = 3). The studies revealed that the prepared Mg-Al mixed oxides are good candidates as support materials for Co-based catalysts. However, interestingly, the support composition does not influence the activity of Ba/Co/Mg-Al catalysts. The change in Mg/Al molar ratio in the range of 2&ndash;5 did not significantly change the catalyst properties. All the catalysts are characterized by similar textural, structural, and chemisorption properties. The similar density of basic sites on the surface of the studied catalysts was reflected in their comparable performance in ammonia synthesis

Influence of the Support Composition on the Activity of Cobalt Catalysts Supported on Hydrotalcite-Derived Mg-Al Mixed Oxides in Ammonia Synthesis

Recently, catalysts with hydrotalcites and hydrotalcite-derived compounds have attracted particular interest due to their specific properties, mostly well-developed texture, high thermal stability, and favorable acid–base properties. In this work, we report the investigation of ammonia synthesis on barium-promoted cobalt catalysts supported on hydrotalcite-derived Mg-Al mixed oxides with different Mg/Al molar ratios. The obtained catalysts were characterized using TGA-MS, nitrogen physisorption, XRPD, TEM, STEM-EDX, H2-TPD, CO2-TPD, and tested in ammonia synthesis (470 °C, 6.3 MPa, H2/N2 = 3). The studies revealed that the prepared Mg-Al mixed oxides are good candidates as support materials for Co-based catalysts. However, interestingly, the support composition does not influence the activity of Ba/Co/Mg-Al catalysts. The change in Mg/Al molar ratio in the range of 2–5 did not significantly change the catalyst properties. All the catalysts are characterized by similar textural, structural, and chemisorption properties. The similar density of basic sites on the surface of the studied catalysts was reflected in their comparable performance in ammonia synthesis

An internal thioester in a pathogen surface protein mediates covalent host binding

To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions