Identifying Antimicrobial Phytocompounds to Combat ISS Superbugs

The isolation, or creation, of novel antimicrobial agents is currently at the forefront of modern healthcare due to the stark decrease in antimicrobial drug development in recent years and due to the increasing rise of superbugs, or microorganisms that are resistant to more than one type of antimicrobial treatment, which are predicted by 2050 to cause 10 million deaths/year. In addition to being a terrestrial cause for concern, antimicrobial resistant microbes are also a threat to the health of the individuals on the International Space Station (ISS). According to recent studies, a diverse population of bacteria and fungi, including several opportunistic pathogens, have colonized the ISS, and many of these strains have been found to possess antimicrobial resistance genes. Therefore, our research is focused on testing bacterial and fungal pathogens that have been isolated from the ISS against methanolic extracts from different medicinal plants, such as Argemone mexicana and Curcuma longa. Additionally, from previous work in our lab (https://doi.org/10.1371/journal.pone.0249704), we have identified several antibacterial compounds in A. mexicana and are attempting to determine the distribution of these phytocompounds (berberine, chelerythrine, sanguinarine) in the plant using quantitative chemistry techniques. This work highlights the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial drug discovery has plateaued

Characterizing the Cytotoxic Effects and Several Antimicrobial Phytocompounds of \u3ci\u3eArgemone mexicana\u3c/i\u3e

Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries by indigenous communities in Mexico and Western parts of the United States. This plant has been exploited to treat a wide variety of ailments, with reported antimicrobial and antioxidant properties, as well as cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the cytotoxic activities of different parts (seeds, leaves, inner vs. outer roots) of the plant from methanol or hexane extracts are preliminarily characterized against cells of seven unique organisms. When comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Additionally, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC (oncogene) and APC (tumor suppressor) mRNA levels help elucidate how the A. mexicana root methanol extract may be affecting colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and subsequent nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, have been identified. The roots were found to possess both phytocompounds, while the leaf lacked chelerythrine

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

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

Elucidating the Antimicrobial Effects of \u3ci\u3eCurcuma longa\u3c/i\u3e, \u3ci\u3eCurcuma aerogunosia\u3c/i\u3e, and \u3ci\u3eZiginber officinale\u3c/i\u3e to Combat Superbugs Related to NASA Space Travel

According to recent studies, the International Space Station has been colonized by numerous bacteria and fungi, including several opportunistic pathogens that have been found to possess antimicrobial resistance. Despite this identified need, there has been a stark decrease in antimicrobial drug development in recent years, which has brought the isolation of novel antimicrobial agents to the forefront of modern healthcare. The increase of antimicrobial-resistant microorganisms, in addition to several scientific reports highlighting how space travel may place astronauts at a heightened risk of infection, has been a driving motivation to discover novel antimicrobial agents. Therefore, the research herein is focused on testing bacterial and fungal pathogens that have been isolated from the International Space Station against methanolic extracts from medicinal plants, such as Curcuma longa, Curcuma aerogunosia, and Ziginber officinale. Methanol extracts from bulbs vs. roots of C. longa, C. aerogunosia, and Z. officinale were separated and tested for antimicrobial activities with several specific extracts showing strong inhibitory effects against multiple bacterial and fungal lines. Further work is currently being conducted to identify the specific compounds responsible for this activity, as well as to better understand the potential mechanism of antimicrobial action. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial drug discovery has plateaued

Characterizing the Cytotoxic Effects and Several Antimicrobial Phytocompounds of Argemone mexicana

Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries to treat a wide variety of ailments. This plant has reported antimicrobial and antioxidant properties, and cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the cytotoxic activities of different A. mexicana plant parts (seeds, leaves, inner vs. outer roots) from methanol or hexane extracts are characterized against cells of seven organisms. Comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Using the MTT colorimetric assay, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC and APC mRNA levels help elucidate how the A. mexicana root methanol extract possibly affects colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, were identified. The roots possessed both phytocompounds, while the leaf lacked chelerythrine. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial and anticancer drug discovery has plateaued

Identifying and Developing Novel Compounds to Combat Superbugs Related to NASA Space Travel

The creation of novel antimicrobial agents is currently at the forefront of modern healthcare due to the stark decrease in antimicrobial drug development in recent years and due to the increasing rise of microorganisms that are resistant to more than one type of antimicrobial treatment, which are predicted by 2050 to cause 10 million deaths/year. In addition to being a terrestrial cause for concern, antimicrobial resistant microbes pose a large threat to the health of individuals during space travel. According to recent studies, numerous bacteria and fungi, including several opportunistic pathogens, have colonized the International Space Station, and many of these strains have been found to possess antimicrobial resistance. Additionally, several scientific reports have highlighted how space travel may alter an astronaut’s immune system, placing them at a heightened risk of infection. Therefore, the research herein is focused on testing bacterial and fungal pathogens that have been isolated from the International Space Station against methanolic extracts from various medicinal plants, such as Argemone mexicana. From previous work by our group, several antibacterial compounds have been isolated from the roots and leaves of A. mexicana, including berberine, chelerythrine and sanguinarine. Ten berberine and three chelerythrine variants of these original phytocompounds have now been synthesized and tested for altered antimicrobial activities. Interestingly, several of these variant compounds show increased antibacterial effects against gram-positive bacteria, yet reduced toxicity against the eukaryotic fungal cell lines tested. Work is currently being conducted to better understand the altered mechanism of action of these promising variant compounds