Perchlorate-Reducing Bacteria from Hypersaline Soils of the Colombian Caribbean

[EN] Perchlorate (ClO4¿) has several industrial applications and is frequently detected in environmental matrices at relevant concentrations to human health. Currently, perchlorate-degrading bacteria are promising strategies for bioremediation in polluted sites. The aim of this study was to isolate and characterize halophilic bacteria with the potential for perchlorate reduction. Ten bacterial strains were isolated from soils of Galerazamba-Bolivar, Manaure-Guajira, and Salamanca Island-Magdalena, Colombia. Isolates grew at concentrations up to 30% sodium chloride. The isolates tolerated pH variations ranging from 6.5 to 12.0 and perchlorate concentrations up to 10000¿mg/L. Perchlorate was degraded by these bacteria on percentages between 25 and 10. 16S rRNA gene sequence analysis indicated that the strains were phylogenetically related to Vibrio, Bacillus, Salinovibrio, Staphylococcus, and Nesiotobacter genera. In conclusion, halophilic-isolated bacteria from hypersaline soils of the Colombian Caribbean are promising resources for the bioremediation of perchlorate contamination.This research received support from the Vice Presidency of Research, University of Cartagena; and Colciencias-University of Cartagena (Grant: RC-758-2011/1107-521-29360).Acevedo-Barrios, R.; Bertel-Sevilla, A.; Alonso Molina, JL.; Olivero-Verbel, J. (2019). Perchlorate-Reducing Bacteria from Hypersaline Soils of the Colombian Caribbean. International Journal of Microbiology. 2019:1-13. https://doi.org/10.1155/2019/6981865S1132019Cole-Dai, J., Peterson, K. M., Kennedy, J. A., Cox, T. S., & Ferris, D. G. (2018). Evidence of Influence of Human Activities and Volcanic Eruptions on Environmental Perchlorate from a 300-Year Greenland Ice Core Record. Environmental Science & Technology, 52(15), 8373-8380. doi:10.1021/acs.est.8b01890Acevedo-Barrios, R., Sabater-Marco, C., & Olivero-Verbel, J. (2018). 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EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Discovery of antiviral molecules for dengue: In silico search and biological evaluation.

Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation

Novel NS2B/NS3-protease dengue virus inhibitors

Dengue disease, caused by the virus of the same name, is expanding globally with an annual estimate of 390 million people infected. However, available antivirals have been ineffective. Therefore, the search of small-molecule therapeutic candidates is a recurrent practice. The dengue virus (DENV) NS2B/NS3 protease complex is a recognized target for the design of specific antivirals, due to its importance in the replication and high degree of sequence conservation. The aim of this research was to find molecules capable of inhibiting this protein complex. A total of 210,903 molecules, from the PubChem database, were docked in silico to the NS2B/NS3 crystallographic structure (PDB: 2FOM). The recombinant protease was expressed in E. coli and purified by affinity chromatography. Five of the best 500 leading compounds, according to the virtual screening affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory activity of these molecules by the protease was evaluated in vitro, using the action of the recombinant enzyme on the Boc-Gly-Arg-Arg-AMC substrate (IC50), and antiviral assays for the detection of NS1 viral titles in infected human hepatocytes. Compounds CID54681617, CID54692801, and CID54715399 showed to be strong inhibitors of NS2B/NS3, with IC50 values (μM) and percentages of NS1 viral title reductions corresponding to 19.9, 79.9%; 17.5, 69.8%; 9.1, 73.9 %, respectively. Multivariate methods on molecular descriptors showed that two of these compounds are structurally different from DENV inhibitors reported by other authors. This discovery opens new possibilities to obtain drug candidates against Dengue.Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias5507-543-31904Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombianan

Discovery of antiviral molecules for dengue: in silico search and biological evaluation

Background: Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. Methods: NS2B/NS3 protease complex structural information was employed to find small molecules that can inhibit the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrateand the complex NS2B/NS3 obtained by recombinant DNA techniques, for testing the activity against dengue virus replication, HepG2 cells infected with dengue virus serotype 2 were used. Results: A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that could inhibit this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. Conclusions: Chemicals CID54681617, CID54692801 and CID54715399 were strong inhibitors of NS2B/NS3, with IC50 values (μM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9 %, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. General significance: This discovery opens new possibilities for obtaining drug candidates against Dengue virus.Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias5507-543-31904Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombianan

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): Study protocol for a multicentre, observational trial

Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369.