Synthesis of Sialic Acid Derivative for Modifying Cell Surface Sialylation

The exterior of cell surfaces express a dense layer of glycans which are often terminated by sialic acid (SA). SA is an acidic monosaccharide whose presence is found on the terminal ends of glycans of either glycoproteins or glycolipids. Due to its hydrophilic and electronegative nature, SA is often involved in both physiological and pathological processes, such as in regulating cellular interactions with ligands, microbes and neighboring cells. In addition to these functions, SA is also implicated in controlling cellular activation, differentiation, transformation and migration. Cell surface glycometabolic engineering provides a useful tool to remodel cell surface SA. In this study, a di-methyl amide derivative of SA, which lacks anionic character, was designed and synthesized for modulation of cell surface SA application. By treating cells with this amide derivative of SA, it is possible to modify the native SA expressed on the cell surface (sialylation status) and study the functions of cell surface SA. The di-methyl amide derivative of SA is synthesized from free SA via benzyl-O-sialoside, amidation and hydrogenation in 6 steps. We hope that the di-methyl amide derivative of SA will provide information regarding the specific mechanisms that are involved in SA biosynthesis and binding events as well as possible cellular consequence due to SA derivation. Eventually, by modifying the cell surface sialylation status, it may be possible to modify cellular functions.https://engagedscholarship.csuohio.edu/u_poster_2018/1030/thumbnail.jp

Sialidase Inhibitors with Different Mechanisms

Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By desialylation, sialidase can modulate the functionality of the target compound and is thus often involved in biological pathways. Inhibition of sialidases with inhibitors is an important approach for under-standing sialidase function and the underlying mechanisms and could serve as a therapeutic approach as well. Transition-state analogues, such as anti-influenza drugs oseltamivir and zanamivir, are major sialidase inhibitors. In addition, difluoro-sialic acids were developed as mechanism-based sialidase inhibitors. Further, fluorinated quinone methide-based suicide substrates were reported. Sialidase product analogue inhibitors were also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, and human sialidases. This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitors, and natural product inhibitors

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Synthesis of Sialic Acid Derivative for Modifying Cell Surface Sialylation

The exterior of cell surfaces express a dense layer of glycans which are often terminated by sialic acid (SA). SA is an acidic monosaccharide whose presence is found on the terminal ends of glycans of either glycoproteins or glycolipids. Due to its hydrophilic and electronegative nature, SA is often involved in both physiological and pathological processes, such as in regulating cellular interactions with ligands, microbes and neighboring cells. In addition to these functions, SA is also implicated in controlling cellular activation, differentiation, transformation and migration. Cell surface glycometabolic engineering provides a useful tool to remodel cell surface SA. In this study, a di-methyl amide derivative of SA, which lacks anionic character, was designed and synthesized for modulation of cell surface SA application. By treating cells with this amide derivative of SA, it is possible to modify the native SA expressed on the cell surface (sialylation status) and study the functions of cell surface SA. The di-methyl amide derivative of SA is synthesized from free SA via benzyl-O-sialoside, amidation and hydrogenation in 6 steps. We hope that the di-methyl amide derivative of SA will provide information regarding the specific mechanisms that are involved in SA biosynthesis and binding events as well as possible cellular consequence due to SA derivation. Eventually, by modifying the cell surface sialylation status, it may be possible to modify cellular functions.https://engagedscholarship.csuohio.edu/u_poster_2018/1030/thumbnail.jp

Structures and Energetics of NI\u3csub\u3e3\u3c/sub\u3e and N\u3csub\u3e2\u3c/sub\u3eI\u3csub\u3e4\u3c/sub\u3e

We have applied new methods for performing coupled‐cluster calculations to small molecules containing iodine atoms; specifically, NI3 and N2I4. Because NI3 is known to be very reactive, attempts to measure its thermodynamic properties have been challenging at best. To date, N2I4 has not been isolated, and our results suggest that its isolation will be just as challenging. We find that the ΔH f(NI3)=+307.7 kJ mol−1 and ΔH f(N2I4)=+551.6 kJ mol−1, confirming that they are unstable with respect to their decomposition products N2 and I2

Ethical Evaluations of Business Students in an Emerging Market: Effects of Ethical Sensitivity, Cultural Values, Personality, and Religiosity

Business ethics has become a very important concern in global business and understanding the effects of various factors on ethical judgments continues to attract research and practitioner attention. Using the Multidimensional Ethics Scale (MES, Reidenbach and Robin 1988) with its five generally accepted philosophical constructs, and vignettes developed by Cohen et al. (1996), current study investigates the relationship between cultural values, personality, religiosity and the ethical sensitivity of business students. We focus on a rapidly emerging country, Turkey, whose economic environment is similar to that of the most Western nations but with a significantly different background and cultural values. Data (n = 184) for the study is collected from a major university in the southeastern Turkey. Although some significant relationships are identified between ethical sensitivity and cultural values and personality, our study findings confirm that MES dimensions had the highest influence on ethical sensitivity levels of business students