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  1. Advanced Dome cellulose/alginate/chitosan composite matrix design with gastric and intestinal co-targeting capacities
    Razali S, Bose A, Benetti C, Chong PW, Miller M, Colombo P, et al.
    Int J Pharm, 2022 Nov 25;628:122226.
    PMID: 36191818 DOI: 10.1016/j.ijpharm.2022.122226
    Dome matrix was designed with gastric and intestinal targeting capacities using melatonin and caffeine as model drugs, and alginate, chitosan and cellulose as composite materials. The melatonin, caffeine and intermediate hydroxypropylmethylcelluose-based dispersible modules were prepared through compaction. Caffeine piled module was capped at both ends with melatonin void modules via intermediate dispersible modules into Dome matrix. Dispersion of intermediate module detached melatonin module from Dome matrix and had it floated in stomach providing a more complete melatonin release due to favorable pH-pKa relationship of dissolution medium and drug. With reference to the caffeine module, the detachment of melatonin module facilitated its gastrointestinal transit as a reduced size matrix, with majority of caffeine delivered in colon. The dual site-targeted and -release Dome matrix is applicable as reference oral carrier for pharmaceutical, nutraceutical, functional food and veterinary medicine where a complex formulation and performancein vivoare required.
  2. Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis
    Lange B, Khan P, Kalmambetova G, Al-Darraji HA, Alland D, Antonenka U, et al.
    Int J Tuberc Lung Dis, 2017 05 01;21(5):493-502.
    PMID: 28399963 DOI: 10.5588/ijtld.16.0702
    SETTING: Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis.

    DESIGN: Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated.

    RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples.

    CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.

  3. Fulltext Zürich II Statement on Per- and Polyfluoroalkyl Substances (PFASs): Scientific and Regulatory Needs
    DeWitt JC, Glüge J, Cousins IT, Goldenman G, Herzke D, Lohmann R, et al.
    Environ Sci Technol Lett, 2024 Aug 13;11(8):786-797.
    PMID: 39156923 DOI: 10.1021/acs.estlett.4c00147
    Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic organic chemicals of global concern. A group of 36 scientists and regulators from 18 countries held a hybrid workshop in 2022 in Zürich, Switzerland. The workshop, a sequel to a previous Zürich workshop held in 2017, deliberated on progress in the last five years and discussed further needs for cooperative scientific research and regulatory action on PFASs. This review reflects discussion and insights gained during and after this workshop and summarizes key signs of progress in science and policy, ongoing critical issues to be addressed, and possible ways forward. Some key take home messages include: 1) understanding of human health effects continues to develop dramatically, 2) regulatory guidelines continue to drop, 3) better understanding of emissions and contamination levels is needed in more parts of the world, 4) analytical methods, while improving, still only cover around 50 PFASs, and 5) discussions of how to group PFASs for regulation (including subgroupings) have gathered momentum with several jurisdictions proposing restricting a large proportion of PFAS uses. It was concluded that more multi-group exchanges are needed in the future and that there should be a greater diversity of participants at future workshops.
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