Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID­19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Collateral vein dynamics in mouse models of venous thrombosis: Pathways consistent with humans.

INTRODUCTION: Prolific collateralization in the venous system has been associated with more severe disease. However, there is a scarcity of information on venogenesis and collateral vessel progression over time. Further, little is understood regarding the relevance of the most common preclinical model-the mouse-for studying venous collateralization. The purpose of this work was to non-invasively and quantitatively characterize collateral vein development and progression in two murine models of deep vein thrombosis using magnetic resonance imaging (MRI). METHODS: Venous thrombosis (VT) was induced in 12-14-week-old male C57BL/6 mice using either the inferior vena cava (IVC) ligation model (n = 5) or the electrolytic IVC model (n = 5). Magnetic Resonance Imaging (MRI) methods optimized for small venous imaging were used on days 2, 6, 14, and 21 following venous thrombosis induction to quantify collateral development and thrombus volume. RESULTS: Collateral veins ~150-200 µm in diameter could be tracked in three dimensions. Collateral pathways were influenced by pre-existing anatomy; mice with bilateral IVC branches showed a predominant superficial collateral pathway (superficial and internal epigastric veins), whereas mice with no lateral branches exhibited a strong intermediate collateral pathway (gonadal and periureteric veins) and were less likely to develop ascending lumbar collaterals. The degree of venogenesis showed a positive correlation with thrombus volume in both models (combined R2 = 0.64, p < 0.0001). CONCLUSIONS: Venous collateral pathways in C57BL/6 mice are consistent with those described in humans. Collateral pathways are influenced by pre-existing anatomy, and the degree of collateralization correlates with thrombus volume.

Sequence and centromere proximal location of a transformation enhancing fragment ans1 from Aspergillus nidulans.

The Aspergillus nidulans sequence ans1, previously known to enhance transformation frequencies of pyr4-based vectors, was shown to enhance the efficiency of argB and trpC-based vectors. Increased efficiencies could be obtained by constructing vectors containing argB and ans1 or by cotransforming selectable plasmids (containing argB, trpC, or pyr4) with the non-selectable ans1 sequence. The preponderance of evidence suggests that the mechanism of ans1 activity does not involve homologous recombination events, in spite of the presence of multiple regions of homology in the A. nidulans genome. Genetic mapping localized ans1 to the vicinity of the centromere of linkage group I. The nucleotide sequence of a 1.8 Kb functional subclone of ans1 was determined and found to be highly A + T rich (81%).

Trimethoprim-rifampin, a new combination agent: efficacy in localized urinary infection and influence on microflora.

Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.