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Clinical Microbiology and Infection :... Jul 2024We aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France. (Observational Study)
Observational Study
OBJECTIVES
We aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France.
METHODS
We included incident cases of cryptococcosis in HIV-seronegative individuals from 2005 to 2020. We compared patient characteristics, disease presentations, cryptococcal antigen results, and induction antifungal treatments according to underlying disease. We examined factors associated with 90-day mortality. Among patients with disseminated infections, we investigated whether receipt of flucytosine and polyene combination was associated with lower mortality.
RESULTS
Among 652 individuals, 209 (32.1%) had malignancy, 130 (19.9%) were solid-organ transplant recipients, 204 (31.3%) had other immunocompromising conditions, and 109 (16.7%) had no reported underlying factor. The commonest presentations were disseminated infections (63.3%, 413/652) and isolated pulmonary infections (25.3%, 165/652). Solid-organ transplant patients were most likely to have disseminated infections and a positive serum cryptococcal antigen result. Patients with malignancy were older and less likely to receive a flucytosine-containing regimen for disseminated infections than others (58.7%, 78/133 vs. 73.2%, 194/265; p 0.029). The crude 90-day case-fatality ratio was 27.2% (95% CI, 23.5%-31.1%). Age ≥60 years (aOR: 2.75 [1.78-4.26]; p < 0.001), meningitis/fungaemia (aOR: 4.79 [1.80-12.7]; p 0.002), and malignancy (aOR: 2.4 [1.14-5.07]; p 0.02) were associated with higher 90-day mortality. Receipt of flucytosine and polyene combination was associated with lower 90-day mortality (aOR: 0.40 [0.23-0.71]; p 0.002) in multivariable analysis and inverse probability of treatment weighted analysis (aOR: 0.45 [0.25-0.80]; p 0.006).
DISCUSSION
HIV-seronegative individuals with cryptococcosis comprise a wide range of underlying conditions with different presentations and outcomes, requiring a tailored approach to diagnosis and management.
Topics: Humans; France; Female; Male; Cryptococcosis; Middle Aged; Adult; Cross-Sectional Studies; Antifungal Agents; Aged; Flucytosine; HIV Seronegativity; Polyenes; Young Adult; Immunocompromised Host
PubMed: 38556212
DOI: 10.1016/j.cmi.2024.03.031 -
Journal of Controlled Release :... Sep 2022Safer and efficacious Amphotericin B (AmB) nanoformulations can be designed by augmenting AmB in the monomeric or super-aggregated state, and restricting the aggregated...
Safer and efficacious Amphotericin B (AmB) nanoformulations can be designed by augmenting AmB in the monomeric or super-aggregated state, and restricting the aggregated state, by choosing the appropriate excipient, which can be facilitated by employing in-silico prediction as a tool. Excipients selected for the study included linear fatty acids from caprylic (C) to stearic(C) and the stearate based amphiphilic surfactants polyoxyl-15-hydroxystearate (PS15) and polyoxyl-40-stearate (PS40). Blend module was employed to determine the two miscibility parameters mixing energy (E) and interaction parameter (χ). AmB-excipient interactions were modelled using molecular docking software. The fatty acids revealed a decrease in E and χ values with increase in carbon chain length, suggesting enhanced affinity with increase in fatty acid hydrophobicity. Significantly higher affinity was observed with amphiphilic surfactants, in particular PS40 which exhibited negative values of E and χ proposing very high degree of miscibility. Molecular docking study confirmed extensive interaction of all the excipients with the AmB polyene chain. PS15 and PS40 displayed in addition hydrophilic interactions with the mycosamine and polyol moieties with PS40 exhibiting complete wrapping of the AmB molecule. PS15 demonstrated only partial wrapping, attributed to the shorter ethylene oxide chain. AmB nanosuspensions (NS) were prepared by in situ nanoprecipitation using the excipients and the AmB state identified by UV scanning between 300-500 nm. AmB NS with fatty acids and PS15-AmB NS revealed a high intensity peak between 330-350 nm of aggregated AmB and low intensity monomeric peaks between 405-415 nm reflecting predominance of the aggregated state. PS40-AmB NS on the other hand revealed complete absence of aggregated state and a high intensity peak between 321-325 nm which corresponded to the super-aggregated state. Also, the super-aggregated state slowly released the safe monomeric form without aggregate formation. Furthermore, very low hemolysis seen with PS40-AmB NS confirmed low toxicity attributed to the safer super-aggregated state and while higher hemolysis as anticipated was seen with PS15-AmB NS (aggregated state). The basis for selection of the appropriate excipient for design of safer AmB nanoformulations would be those excipients that exhibit negative values of miscibility parameters E and χ, exhibit interaction with the hydrophobic and hydrophilic regions of AmB and demonstrate complete wrapping of AmB in the molecular docking study. Our study thus demonstrates feasibility of in-silico prediction as a practical tool for excipient selection for safer AmB nanoformulations.
Topics: Amphotericin B; Antifungal Agents; Carbon; Ethylene Oxide; Excipients; Hemolysis; Humans; Molecular Docking Simulation; Polyenes; Polyethylene Glycols; Stearates; Surface-Active Agents
PubMed: 35905782
DOI: 10.1016/j.jconrel.2022.07.030 -
Nature Chemical Biology Nov 2020
Topics: Polyenes; Polyketides; Polyunsaturated Alkamides; Tumor Suppressor Protein p53
PubMed: 32572276
DOI: 10.1038/s41589-020-0586-x -
Biochimica Et Biophysica Acta.... Feb 2019The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering... (Review)
Review
The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering anti-fungal agents with new mechanisms of action and on optimizing the use of existing agents. In this context, interest in the polyene group of anti-fungals has recently been renewed, since they are known to be effective against a broad spectrum of fungal pathogens that only rarely develop a resistance to them. In the past 10 years considerable efforts have been made to improve their efficacy and, simultaneously, to reduce their toxicity. Knowledge about the basic mechanisms of their action will be of crucial importance to further optimizing their use. The mechanisms of polyene action at the membrane level are reviewed here, focusing primarily on their pore-forming activity and on the resulting osmotic responses of artificial lipid vesicles and different eukaryotic cells.
Topics: Antifungal Agents; Lipids; Membranes, Artificial; Polyenes; Porosity
PubMed: 30458121
DOI: 10.1016/j.bbamem.2018.11.006 -
Nature Reviews. Drug Discovery Jan 2024
Topics: Humans; Antifungal Agents; Polyenes
PubMed: 38040792
DOI: 10.1038/d41573-023-00196-5 -
Nature Chemistry Jan 2023The cis/trans geometry of olefins is known to dramatically influence the thermal and mechanical properties of polyalkenamers. Yet, polymerization methods that...
The cis/trans geometry of olefins is known to dramatically influence the thermal and mechanical properties of polyalkenamers. Yet, polymerization methods that efficiently control this parameter are scarce. Here we report the development of a stereoretentive acyclic diene metathesis polymerization that uses the reactivity of dithiolate Ru carbenes combined with cis monomers. These Ru catalysts exhibit exquisite retention of the cis geometry and tolerate many polar functional groups, enabling the synthesis of all-cis polyesters, polycarbonates, polyethers and polysulfites. The stereoretentive acyclic diene metathesis polymerization is also characterized by low catalyst loadings and tolerance towards trans impurities in the monomer batch, which should facilitate large-scale implementation. Modulation of the reaction temperature and time leads to an erosion of stereoretention, permitting a stereocontrolled synthesis of polyalkenamers with predictable cis:trans ratios. The impact of the stereochemistry of the repeating alkenes on the thermal properties is clearly demonstrated through differential scanning calorimetry and thermogravimetric analysis.
Topics: Polymerization; Polyenes; Alkenes; Temperature; Catalysis
PubMed: 36280767
DOI: 10.1038/s41557-022-01060-6 -
World Journal of Microbiology &... Jun 2021Accumulation of plastic wastes and their effects on the ecosystem have triggered an alarm regarding environmental damage, which explains the massive investigations over... (Review)
Review
Accumulation of plastic wastes and their effects on the ecosystem have triggered an alarm regarding environmental damage, which explains the massive investigations over the past few years, aiming technological alternatives for their proper destination and valorization. In this context, biological degradation emerges as a green route for plastic processing and recycling in a circular economy approach. Some of the main polymers produced worldwide are poly(ethylene terephthalate) (PET), polyethylene (PE) and polypropylene (PP), which are among the most recalcitrant materials in the environment. In comparison to other polymers, PET biodegradation has advanced dramatically in recent years concerning microbial and enzymatic mechanisms, being positioned in a higher technology readiness level (TRL). Even more challenging, polyolefins (PE and PP) biodegradation is hindered by their high recalcitrance, which is mainly related to stable carbon-carbon bonds. Potential microbial biocatalysts for this process have been evaluated, but the related mechanisms are still not fully elucidated. This review aims to discuss the latest developments on key microbial biocatalysts for degradation of these polymers, addressing biodegradation monitoring, intellectual property, and TRL analysis of the bioprocessing strategies using biodegradation performance, process time and scale as parameters for the evaluation.
Topics: Biocatalysis; Biodegradation, Environmental; Ecosystem; Plastics; Polyenes; Polyethylene Terephthalates; Recycling
PubMed: 34125298
DOI: 10.1007/s11274-021-03089-0 -
Dental Traumatology : Official... Oct 2018Mouthguard sheet materials such as ethylene vinyl acetate and polyolefin have been used commonly. However, the change of the sheet temperature during heating of the... (Comparative Study)
Comparative Study
BACKGROUND/AIM
Mouthguard sheet materials such as ethylene vinyl acetate and polyolefin have been used commonly. However, the change of the sheet temperature during heating of the polyolefin has not been determined. The aim of this study was to examine the change of the sheet temperature during heating and to examine the vacuum-formed mouthguard characteristics for the sheet materials.
MATERIALS AND METHODS
The mouthguard materials used were 4.0-mm sheets of ethylene vinyl acetate and polyolefin. The sheet temperature of the two materials was measured when the center of the sheet was displaced by 10, 15, and 20 mm from the baseline after heating. Sheet temperature differences by sheet materials were analyzed by two-way analysis of variance. The sheets were vacuum-formed when the heating temperatures reached 100°C using ethylene vinyl acetate sheet and polyolefin sheet. Mouthguard thickness and fit was measured at the central incisor and the first molar. Differences in the thickness and fit between the sheet materials were analyzed by two-way analysis of variance.
RESULTS
The sheet temperature of ethylene vinyl acetate sheets became higher as the hanging distance became larger (P < 0.05), but that of polyolefin sheets was not different. The thicknesses of the vacuum-formed mouthguard at the central incisor and the first molar were greater in the mouthguards formed by ethylene vinyl acetate sheets than that with polyolefin sheets (P < 0.01 or P < 0.05). The fit of the mouthguard was not different between mouthguards formed by ethylene vinyl acetate sheets and that formed by polyolefin sheets.
CONCLUSIONS
The change of mouthguard sheet temperature during heating was different between ethylene vinyl acetate and polyolefin sheets. The ethylene vinyl acetate sheets maintained the vacuum-formed mouthguard thickness in comparison with the polyolefin sheets with a better fit.
Topics: Equipment Design; Hot Temperature; Humans; Materials Testing; Mouth Protectors; Polyenes; Vacuum; Vinyl Compounds
PubMed: 29920939
DOI: 10.1111/edt.12422 -
Analytical Chemistry Oct 2022Dinoflagellate-derived polyketides are typically large molecules (>1000 Da) with complex structures, potent bioactivities, and high toxicities. Their discovery suffers...
Dinoflagellate-derived polyketides are typically large molecules (>1000 Da) with complex structures, potent bioactivities, and high toxicities. Their discovery suffers three major bottlenecks: insufficient bioavailability, low-yield cultivation of producer organisms, and production of multiple highly related analogues by a single strain. Consequently, the biotechnological production of therapeutics or toxicological standards of dinoflagellate-derived polyketides is also hampered. Strategies based on sensitive and selective techniques for chemical prospection of dinoflagellate extracts could aid in overcoming these limitations, as it allows selecting the most interesting candidates for discovery and exploitation programs according to the biosynthetic potential. In this work, we assess the combination of data-dependent liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS) and molecular networking to screen polyol polyketides. To demonstrate the power of this approach, we selected dinoflagellate since it is commonly used as a biotechnological model and produces amphidinols, a family of polyol-polyene compounds with antifungal and antimycoplasmal activity. First, we screened families of compounds with multiple hydroxyl groups by examining MS profiles that contain sequential neutral losses of water. Then, we clustered MS spectra by molecular networking to facilitate the dereplication and discovery of amphidinols. Finally, we used the MS fragmentation behavior of well-characterized luteophanol D as a model to propose a structural hypothesis of nine novel amphidinols. We envision that this strategy is a valuable approach to rapidly monitoring toxin production of known and unknown polyol polyketides in dinoflagellates, even in small culture volumes, and distinguishing strains according to their toxin profiles.
Topics: Antifungal Agents; Dinoflagellida; Polyenes; Polyketides; Polymers; Water
PubMed: 36190828
DOI: 10.1021/acs.analchem.2c02185 -
The Journal of Experimental Biology Jun 2020Parrots and allies (Order Psittaciformes) have evolved an exclusive capacity to synthesize polyene pigments called psittacofulvins at feather follicles, which allows...
Parrots and allies (Order Psittaciformes) have evolved an exclusive capacity to synthesize polyene pigments called psittacofulvins at feather follicles, which allows them to produce a striking diversity of pigmentation phenotypes. Melanins are polymers constituting the most abundant pigments in animals, and the sulphurated form (pheomelanin) produces colors that are similar to those produced by psittacofulvins. However, the differential contribution of these pigments to psittaciform phenotypic diversity has not been investigated. Given the color redundancy, and physiological limitations associated with pheomelanin synthesis, we hypothesized that the latter would be avoided by psittaciform birds. Here, we tested this using Raman spectroscopy to identify pigments in feathers exhibiting colors suspected of being produced by pheomelanin (i.e. dull red, yellow, greyish-brown and greenish-brown) in 26 species from the three main lineages of Psittaciformes. We detected the non-sulphurated melanin form (eumelanin) in black, grey and brown plumage patches, and psittacofulvins in red, yellow and green patches, but there was no evidence of pheomelanin. As natural melanins are assumed to be composed of eumelanin and pheomelanin in varying ratios, our results represent the first report of impairment of mixed melanin-based pigmentation in animals. Given that psittaciforms also avoid the uptake of circulating carotenoid pigments, these birds seem to have evolved a capacity to avoid functional redundancy between pigments, likely by regulating follicular gene expression. Our study provides the first vibrational characterization of different psittacofulvin-based colors and thus helps to determine the relative polyene chain length in these pigments, which is related to their antireductant protection activity.
Topics: Animals; Carotenoids; Feathers; Melanins; Parrots; Pigmentation
PubMed: 32393547
DOI: 10.1242/jeb.225912