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Durham Todd posted an update 6 months ago
Infection with hepatitis C virus (HCV) remains a major cause of morbidity and mortality worldwide despite the recent advent of highly effective direct-acting antivirals. The envelope glycoproteins of HCV are heavily glycosylated with a high proportion of high-mannose glycans (HMGs), which serve as a shield against neutralizing antibodies and assist in the interaction with cell-entry receptors. However, there is no approved therapeutic targeting this potentially druggable biomarker.
The anti-HCV activity of a fusion protein consisting of Avaren lectin and the fragment crystallizable (Fc) region of a human immunoglobulin G1 antibody, Avaren-Fc (AvFc) was evaluated through the use of invitro neutralization assays as well as an invivo challenge in a chimeric human liver (PXB) mouse model. Drug toxicity was assessed by histopathology, serum alanine aminotransferase, and mouse body weights.
AvFc was capable of neutralizing cell culture-derived HCV in a genotype-independent manner, with 50% inhibitory concentr patients.Coronary artery bypass grafting (CABG) is the standard treatment modality in revascularization of the myocardium. However, the graft failure remains the major complication following CABG procedure. Involvement of mitochondrial damage-associated molecular patterns (mt-DAMPs) in the pathogenesis of vein-graft failure is largely unknown. Here, we investigated the expression of major protein-mt-DAMPs, cytochrome-C (Cyt-C), heat shock protein-60 (Hsp-60), mitochondrial transcription factor A (mtTFA), in the occluded graft and associated tissues, including distal left anterior descending (LAD), LAD adjacent to anastomosis, and left internal mammary artery (LIMA) in the microswine CABG model. The protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) was significantly decreased in the graft and LIMA, whereas the protein expression of hypoxia inducible factor-1 alpha (HIF-1α) and Cyt-C was decreased and that of mtTFA and Hsp60 was increased in all tissues compared to controls. There was no significant difference in the protein expression of citrate synthase, complex-1, and mitochondrial pyruvate dehydrogenase in the graft and associated tissues compared to control. Hypoxia in cultured smooth muscle cells (SMCs) significantly upregulated all mitochondrial biomarkers and mt-DAMPs compared to normoxia. The increased reactive oxygen species (ROS) content and compromised membrane integrity in the hypoxic SMCs correlated well with increased mt-DAMPs in the graft and associated tissues, suggesting a possible role of mt-DAMPs in the pathogenesis of graft failure. These findings suggest that the pathological signals elicited by mt-DAMPs could reveal targets for better therapeutic approaches and diagnostic strategies in the management of CABG graft failure.
Chronic viral hepatitis (CVH) is a leading contributor to the UK liver disease epidemic, with global migration from high prevalence areas (e.g., South Asia). Despite international guidance for testing high-risk groups in line with elimination targets, there is no consensus on how to achieve this. The objectives of this study were to assess the following (1) the feasibility of recruiting South Asian migrants to view an educational film on CVH, (2) the effectiveness of the film in promoting testing and increasing knowledge of CVH, and (3) the methodological issues relevant to scale-up to a randomized controlled trial.
South Asian migrants were recruited to view the film (intervention) in community venues (primary care, religious, community), with dried blood spot CVH testing offered immediately afterwards. Pre/post-film questionnaires assessed the effectiveness of the intervention.
Two hundred and nineteen first-generation migrants ≥18 years of age (53% female) were recruited to view the film at the follomigrants to view a community-based educational film promoting CVH testing in this higher risk group, confirming the value of developing interventions to facilitate the global World Health Organization plan for targeted case finding and elimination, and a future randomized controlled trial. We highlight the importance of culturally relevant interventions including faith and culturally sensitive settings, which appear to minimize logistical issues and effectively engage minority groups, allowing ease of access to individuals ‘at risk’.
Face masks are an important component of personal protection equipment employed in preventing the spread of diseases such as COVID-19. As the supply of mass-produced masks has decreased, the use of homemade masks has become more prevalent. It is important to quantify the effectiveness of different types of materials to provide useful information, which should be considered for homemade masks.
Filtration effects of different types of common materials were studied by measuring the aerosol droplet concentrations in the upstream and downstream regions. Flow-field characteristics of surrounding regions of tested materials were investigated using a laser-diagnostics technique, i.e., particle image velocimetry. Amoxanox The pressure difference across the tested materials was measured.
Measured aerosol concentrations indicated a breakup of large-size particles into smaller particles. Tested materials had higher filtration efficiency for large particles. Single-layer materials were less efficient, but they had a low pressure-drop. Multilayer materials could produce greater filtering efficiency with an increased pressure drop, which is an indicator of comfort level and breathability. The obtained flow-fields indicated a flow disruption downstream of the tested materials as the velocity magnitude noticeably decreased.
The obtained results provide an insight into flow-field characteristics and filtration efficiency of different types of household materials commonly used for homemade masks. This study allows comparison with mass-produced masks under consistent test conditions while employing several well-established techniques.
The obtained results provide an insight into flow-field characteristics and filtration efficiency of different types of household materials commonly used for homemade masks. This study allows comparison with mass-produced masks under consistent test conditions while employing several well-established techniques.