Search Results (6)

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2. Full article

The ability of each new SARS-CoV-2 variant to evade host humoral immunity is the focus of intense research. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here, we demonstrate a new approach to assessing viral replication kinetics using real-time cell analysis (RTCA). Virus-induced cell death is measured in real time as changes in electrical impedance through cell monolayers while images are acquired at defined intervals via an onboard microscope and camera. Using this system, we quantified replication kinetics of five clinically important viral variants: WA1/2020 (ancestral), Delta, and Omicron subvariants BA.1, BA.4, and BA.5. Multiple measures proved useful in variant replication comparisons, including the elapsed time to, and the slope at, the maximum rate of cell death. Important findings include significantly weaker replication kinetics of BA.1 by all measures, while BA.5 harbored replication kinetics at or near ancestral levels, suggesting evolution to regain replicative capacity, and both an altered profile of cell killing and enhanced fusogenicity of the Delta variant. Together, these data show that RTCA is a robust method to assess replicative capacity of any given SARS-CoV-2 variant rapidly and quantitatively, which may be useful in assessment of newly emerging variants. Full article

Hydrogen peroxide, povidone-iodine, and chlorhexidine are antiseptics that are commonly added to irrigants to either prevent or treat infection. There are little clinical data available that demonstrate efficacy of adding antiseptics to irrigants in the treatment of periprosthetic joint infection after biofilm establishment. The objective of the study was to assess the bactericidal activity of the antiseptics on S. aureus planktonic and biofilm. For planktonic irrigation, S. aureus was exposed to different concentrations of antiseptics. S. aureus biofilm was developed by submerging a Kirschner wire into normalized bacteria and allowing it to grow for forty-eight hours. The Kirschner wire was then treated with irrigation solutions and plated for CFU analysis. Hydrogen peroxide, povidone-iodine, and chlorhexidine were bactericidal against planktonic bacteria with over a 3 log reduction (p < 0.0001). Unlike cefazolin, the antiseptics were not bactericidal (less than 3 log reduction) against biofilm bacteria but did have a statistical reduction in biofilm as compared to the initial time point (p < 0.0001). As compared to cefazolin treatment alone, the addition of hydrogen peroxide or povidone-iodine to cefazolin treatment only additionally reduced the biofilm burden by less than 1 log. The antiseptics demonstrated bactericidal properties with planktonic S. aureus; however, when used to irrigate S. aureus biofilms, these antiseptics were unable to decrease biofilm mass below a 3 log reduction, suggesting that S. aureus biofilm has a tolerance to antiseptics. This information should be considered when considering antibiotic tolerance in established S. aureus biofilm treatment. Full article

Multidisciplinary team (MDT) meetings are the mainstay of the decision-making process for patients presenting with complex clinical problems such as papillary thyroid carcinoma (PTC). Adherence to guidelines by MDTs has been extensively investigated; however, scarce evidence exists on MDT performance and variability where guidelines are less prescriptive. We evaluated the consistency of MDT management recommendations for T1 and T2 PTC patients and explored key variables that may influence therapeutic decision making. A retrospective review of the prospective database of all T1 and T2 PTC patients discussed by the MDT was conducted between January 2016 and May 2021. Univariate analysis (with Bonferroni correction significance calculated at p < 0.006) was performed to establish clinical variables linked to completion thyroidectomy and Radioactive iodine (RAI) recommendations. Of 468 patients presented at thyroid MDT, 144 pT1 PTC and 118 pT2 PTC met the selection criteria. Only 18% (n = 12) of pT1 PTC patients initially managed with hemithyroidectomy were recommended completion thyroidectomy. Mean tumour diameter was the only variable differing between groups (p = 0.003). pT2 patients were recommended completion thyroidectomy in 66% (n = 16) of instances. No measured variable explained the difference in recommendation. pT1 patients initially managed with total thyroidectomy were not recommended RAI in 71% (n = 55) of cases with T1a status (p = 0.001) and diameter (p = 0.001) as statistically different variables. For pT2 patients, 60% (n = 41) were recommended RAI post-total thyroidectomy, with no differences observed among groups. The majority of MDT recommendations were concordant for patients with similar measurable characteristics. Discordant recommendations for a small group of patients were not explained by measured variables and may have been accounted for by individual patient factors. Further research into the MDT decision-making process is warranted. Full article

The Actinomycetales order is one of great genetic and functional diversity, including diversity in the production of secondary metabolites which have uses in medical, environmental rehabilitation, and industrial applications. Secondary metabolites produced by actinomycete species are an abundant source of antibiotics, antitumor agents, anthelmintics, and antifungals. These actinomycete-derived medicines are in circulation as current treatments, but actinomycetes are also being explored as potential sources of new compounds to combat multidrug resistance in pathogenic bacteria. Actinomycetes as a potential to solve environmental concerns is another area of recent investigation, particularly their utility in the bioremediation of pesticides, toxic metals, radioactive wastes, and biofouling. Other applications include biofuels, detergents, and food preservatives/additives. Exploring other unique properties of actinomycetes will allow for a deeper understanding of this interesting taxonomic group. Combined with genetic engineering, microbial experimental evolution, and other enhancement techniques, it is reasonable to assume that the use of marine actinomycetes will continue to increase. Novel products will begin to be developed for diverse applied research purposes, including zymology and enology. This paper outlines the current knowledge of actinomycete usage in applied research, focusing on marine isolates and providing direction for future research. Full article

Extreme summertime heat is a significant public health threat that disproportionately impacts vulnerable urban populations. Research on health impacts of climate change (including increasing intensity, duration, and frequency of hot weather) is sometimes designed and implemented without the involvement of the communities being studied, i.e., “community-placed” not “community-based.” We describe how the Heatwaves, Housing, and Health: Increasing Climate Resiliency in Detroit (HHH) partnership engaged relevant communities by integrating a community-based participatory research (CBPR) approach into an existing, academic-designed research project through a steering committee of community and academic partners. Using a case study approach, we analyze program documentation, partnership evaluation questionnaires, and HHH steering committee meeting notes. We describe the CBPR process by which we successfully collected research data in Detroit during summer 2016, engaged in collaborative analysis of data, and shared results with Detroit residents. Evaluations of the partnership over 2 years show community involvement in research; enhanced capacities; success in securing new grant funding; and ways that CBPR strengthened the validity, relevance, and translation of research. Engaging communities as equal partners using CBPR, even after a study is underway, can strengthen research to understand and address the impacts of extreme heat on health and equity in urban communities. Full article