Surface-Associated Plasminogen Binding of Cryptococcus neoformans Promotes Extracellular Matrix Invasion

BACKGROUND:The fungal pathogen Cryptococcus neoformans is a leading cause of illness and death in persons with predisposing factors, including: malignancies, solid organ transplants, and corticosteroid use. C. neoformans is ubiquitous in the environment and enters into the lungs via inhalation, where it can disseminate through the bloodstream and penetrate the central nervous system (CNS), resulting in a difficult to treat and often-fatal infection of the brain, called meningoencephalitis. Plasminogen is a highly abundant protein found in the plasma component of blood and is necessary for the degradation of fibrin, collagen, and other structural components of tissues. This fibrinolytic system is utilized by cancer cells during metastasis and several pathogenic species of bacteria have been found to manipulate the host plasminogen system to facilitate invasion of tissues during infection by modifying the activation of this process through the binding of plasminogen at their surface. METHODOLOGY:The invasion of the brain and the central nervous system by penetration of the protective blood-brain barrier is a prerequisite to the establishment of meningoencephalitis by the opportunistic fungal pathogen C. neoformans. In this study, we examined the ability of C. neoformans to subvert the host plasminogen system to facilitate tissue barrier invasion. Through a combination of biochemical, cell biology, and proteomic approaches, we have shown that C. neoformans utilizes the host plasminogen system to cross tissue barriers, providing support for the hypothesis that plasminogen-binding may contribute to the invasion of the blood-brain barrier by penetration of the brain endothelial cells and underlying matrix. In addition, we have identified the cell wall-associated proteins that serve as plasminogen receptors and characterized both the plasminogen-binding and plasmin-activation potential for this significant human pathogen. CONCLUSIONS:The results of this study provide evidence for the cooperative role of multiple virulence determinants in C. neoformans pathogenesis and suggest new avenues for the development of anti-infective agents in the prevention of fungal tissue invasion

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Aconitic Acid Recovery from Renewable Feedstock and Review of Chemical and Biological Applications

Aconitic acid (propene-1,2,3-tricarboxylic acid) is the most prevalent 6-carbon organic acid that accumulates in sugarcane and sweet sorghum. As a top value-added chemical, aconitic acid may function as a chemical precursor or intermediate for high-value downstream industrial and biological applications. These downstream applications include use as a bio-based plasticizer, cross-linker, and the formation of valuable and multi-functional polyesters that have also been used in tissue engineering. Aconitic acid also plays various biological roles within cells as an intermediate in the tricarboxylic acid cycle and in conferring unique survival advantages to some plants as an antifeedant, antifungal, and means of storing fixed pools of carbon. Aconitic acid has also been reported as a fermentation inhibitor, anti-inflammatory, and a potential nematicide. Since aconitic acid can be sustainably sourced from renewable, inexpensive sources such as sugarcane, molasses, and sweet sorghum syrup, there is enormous potential to provide multiple streams of additional income to the sugar industry through downstream industrial and biological applications that we discuss in this review

A Review on the Production of C4 Platform Chemicals from Biochemical Conversion of Sugar Crop Processing Products and By-Products

The development and commercialization of sustainable chemicals from agricultural products and by-products is necessary for a circular economy built on renewable natural resources. Among the largest contributors to the final cost of a biomass conversion product is the cost of the initial biomass feedstock, representing a significant challenge in effective biomass utilization. Another major challenge is in identifying the correct products for development, which must be able to satisfy the need for both low-cost, drop-in fossil fuel replacements and novel, high-value fine chemicals (and/or commodity chemicals). Both challenges can be met by utilizing wastes or by-products from biomass processing, which have very limited starting cost, to yield platform chemicals. Specifically, sugar crop processing (e.g., sugarcane, sugar beet) is a mature industry that produces high volumes of by-products with significant potential for valorization. This review focuses specifically on the production of acetoin (3-hydroxybutanone), 2,3-butanediol, and C4 dicarboxylic (succinic, malic, and fumaric) acids with emphasis on biochemical conversion and targeted upgrading of sugar crop products/by-products. These C4 compounds are easily derived from fermentations and can be converted into many different final products, including food, fragrance, and cosmetic additives, as well as sustainable biofuels and other chemicals. State-of-the-art literature pertaining to optimization strategies for microbial conversion of sugar crop byproducts to C4 chemicals (e.g., bagasse, molasses) is reviewed, along with potential routes for upgrading and valorization. Directions and opportunities for future research and industrial biotechnology development are discussed

A Review on the Production of C4 Platform Chemicals from Biochemical Conversion of Sugar Crop Processing Products and By-Products

The development and commercialization of sustainable chemicals from agricultural products and by-products is necessary for a circular economy built on renewable natural resources. Among the largest contributors to the final cost of a biomass conversion product is the cost of the initial biomass feedstock, representing a significant challenge in effective biomass utilization. Another major challenge is in identifying the correct products for development, which must be able to satisfy the need for both low-cost, drop-in fossil fuel replacements and novel, high-value fine chemicals (and/or commodity chemicals). Both challenges can be met by utilizing wastes or by-products from biomass processing, which have very limited starting cost, to yield platform chemicals. Specifically, sugar crop processing (e.g., sugarcane, sugar beet) is a mature industry that produces high volumes of by-products with significant potential for valorization. This review focuses specifically on the production of acetoin (3-hydroxybutanone), 2,3-butanediol, and C4 dicarboxylic (succinic, malic, and fumaric) acids with emphasis on biochemical conversion and targeted upgrading of sugar crop products/by-products. These C4 compounds are easily derived from fermentations and can be converted into many different final products, including food, fragrance, and cosmetic additives, as well as sustainable biofuels and other chemicals. State-of-the-art literature pertaining to optimization strategies for microbial conversion of sugar crop byproducts to C4 chemicals (e.g., bagasse, molasses) is reviewed, along with potential routes for upgrading and valorization. Directions and opportunities for future research and industrial biotechnology development are discussed

Aconitic Acid Recovery from Renewable Feedstock and Review of Chemical and Biological Applications

Aconitic acid (propene-1,2,3-tricarboxylic acid) is the most prevalent 6-carbon organic acid that accumulates in sugarcane and sweet sorghum. As a top value-added chemical, aconitic acid may function as a chemical precursor or intermediate for high-value downstream industrial and biological applications. These downstream applications include use as a bio-based plasticizer, cross-linker, and the formation of valuable and multi-functional polyesters that have also been used in tissue engineering. Aconitic acid also plays various biological roles within cells as an intermediate in the tricarboxylic acid cycle and in conferring unique survival advantages to some plants as an antifeedant, antifungal, and means of storing fixed pools of carbon. Aconitic acid has also been reported as a fermentation inhibitor, anti-inflammatory, and a potential nematicide. Since aconitic acid can be sustainably sourced from renewable, inexpensive sources such as sugarcane, molasses, and sweet sorghum syrup, there is enormous potential to provide multiple streams of additional income to the sugar industry through downstream industrial and biological applications that we discuss in this review

The Influence of Oxidizing and Non-Oxidizing Biocides on Enzymatic and Microbial Activity in Sugarcane Processing

Processing aids are utilized during raw sugar manufacturing at sugarcane processing facilities to mitigate unwanted contamination from microorganisms and their associated exopolysaccharides (EPS). Microorganisms in processing facilities contribute to sugar losses through sucrose inversion and consumption, with many bacteria strains subsequently producing dextran and fructan EPS that can cause downstream issues related to viscosity and crystallization. Similar issues also result from the presence of unwanted starches from plant material in cane juices. Processing aids include biocides for bacterial inhibition, and enzymes (e.g., dextranase, amylase) to break down polysaccharides in juices. However, oxidizing biocide processing aids (e.g., sodium hypochlorite) may inhibit enzymatic processing aid activity. In this study, biocides (sodium hypochlorite, carbamate, and hop extract) and enzymes (dextranase and amylase) were simultaneously added to sugarcane juice to measure residual enzymatic activity for dextranase and amylase. The same biocides were also tested to estimate minimum inhibitory concentrations against bacterial strains isolated from Louisiana sugarcane processing facilities. These experiments provide evidence to suggest that sodium hypochlorite may interfere with enzymatic processing aid activity, with lesser/limited enzymatic inhibition from carbamates and hop extracts. Biocide susceptibility assays suggest that sodium hypochlorite has limited effectiveness against tested bacterial strains. Hop extract biocide was only effective against Gram-positive Leuconostoc while carbamate biocide showed more broad-spectrum activity against all tested strains