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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.[Prise en charge des exacerbations de la bronchopneumopathie chronique obstructive (BPCO). Recommandations de la Société de pneumologie de langue française (texte court)] La bronchopneumopathie chronique obstructive (BPCO) est la maladie respiratoire chronique dont le poids sur la santé publique est le plus grand par sa morbidité, sa mortalité et les dépenses de santé qu’elle induit. Pour les individus atteints, la BPCO est une source majeure de handicap du fait de la dyspnée, de la limitation d’activité, des exacerbations, du risque d’insuffisance respiratoire chronique et des manifestations extra-respiratoires qu’elle entraîne. Les précédentes recommandations de la Société de pneumologie de langue française (SPLF) sur la prise en charge des exacerbations BPCO date de 2003. Se fondant sur une méthodologie adaptée de GRADE, le présent document propose une actualisation de la question des exacerbations de BPCO en développant un argumentaire couvrant quatre champs d’investigation : (1) épidémiologie, (2) évaluation clinique, (3) prise en charge thérapeutique et (4) prévention. Les modalités spécifiques de la prise en charge hospitalière et ambulatoire y sont discutées, particulièrement les aspects relevant de l’évaluation de la sévérité de l’exacerbation et de la prise en charge pharmacologique

Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

International audienceAbstract Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) ( P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% ( P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed

Correction to: Characteristics and prognosis of bloodstream infection in patients with COVID‑19 admitted in the ICU: an ancillary study of the COVID‑ICU study

International audienc

Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study

International audienceBackground Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate