Quenching of quorum sensing in multi-drug resistant Pseudomonas aeruginosa: insights on halo-bacterial metabolites and gamma irradiation as channels inhibitors.

BACKGROUND: Anti-virulence therapy is a promising strategy to treat multi-drug resistant (MDR) pathogens. Pseudomonas aeruginosa is a potent opportunistic pathogen because of an array of virulence factors that are regulated by quorum sensing systems. METHODS: The virulence features of four multi-drug resistant P. aeruginosa strains were investigated upon exposure to the sub-lethal dose of gamma rays (1 kGy), and sub-inhibitory concentrations of bioactive metabolites recovered from local halophilic strains in comparison to control. Then, the gene expression of AHL-mediated quorum sensing systems (las/rhl) was quantitatively determined in treated and untreated groups by real-time PCR. RESULTS: The bioactive metabolites recovered from halophilic strains previously isolated from saline ecosystems were identified as Halomonas cupida (Halo-Rt1), H. elongate (Halo-Rt2), Vigibacillus natechei (Halo-Rt3), Sediminibacillus terrae (Halo-Rt4) and H. almeriensis (Halo-Rt5). Results revealed that both gamma irradiation and bioactive metabolites significantly reduced the virulence factors of the tested MDR strains. The bioactive metabolites showed a maximum efficiency for inhibiting biofilm formation and rhamnolipids production whereas the gamma irradiation succeeded in decreasing other virulence factors to lower levels in comparison to control. Quantitative-PCR results showed that AHL-mediated quorum sensing systems (las/rhl) in P. aeruginosa strains were downregulated either by halo-bacterial metabolites or gamma irradiation in all treatments except the upregulation of both lasI internal gene and rhlR intact gene in P. aeruginosa NCR-RT3 and both rhlI internal gene and rhlR intact gene in P. aeruginosa U3 by nearly two folds or more upon exposure to gamma irradiation. The most potent result was observed in the expression of lasI internal gene that was downregulated by more than ninety folds in P. aeruginosa NCR-RT2 after treatment with metabolites of S. terrae (Halo-Rt4). Analyzing metabolites recovered from H. cupida (Halo-Rt1) and H. elongate (Halo-Rt2) using LC-ESI-MS/MS revealed many chemical compounds that have quorum quenching properties including glabrol, 5,8-dimethoxyquinoline-2-carbaldehyde, linoleoyl ethanolamide, agelasine, penigequinolones derivatives, berberine, tetracosanoic acid, and liquidambaric lactone in the former halophile and phloretin, lycoctonine, fucoxanthin, and crassicauline A in the latter one. CONCLUSION: QS inhibitors can significantly reduce the pathogenicity of MDR P. aeruginosa strains; and thus can be an effective and successful strategy for treating antibiotic resistant traits.

Comparison of different ratios of propofol-ketamine admixture in rapid-sequence induction of anesthesia for emergency laparotomy: a randomized controlled trial.

BACKGROUND: We aimed to compare the hemodynamic effect of two ratios of propofol and ketamine (ketofol), namely 1:1 and 1:3 ratios, in rapid-sequence induction of anesthesia for emergency laparotomy. METHODS: This randomized controlled study included adult patients undergoing emergency laparotomy under general anesthesia. The patients were randomized to receive either ketofol ratio of 1:1 (n = 37) or ketofol ratio of 1:3 (n = 37). Hypotension (mean arterial pressure < 70 mmHg) was managed by 5-mcg norepinephrine. The primary outcome was total norepinephrine requirements during the postinduction period. Secondary outcomes included the incidence of postinduction hypotension, and the intubation condition (excellent, good, or poor). RESULTS: Thirty-seven patients in the ketofol-1:1 and 35 patients in the ketofol 1:3 group were analyzed. The total norepinephrine requirement was less in the ketofol-1:1 group than in the ketofol-1:3 group, P-values: 0.043. The incidence of postinduction hypotension was less in the ketofol-1:1 group (4 [12%]) than in ketofol-1:3 group (12 [35%]), P-value 0.022. All the included patients had excellent intubation condition. CONCLUSION: In patients undergoing emergency laparotomy, the use of ketofol in 1:1 ratio for rapid-sequence induction of anesthesia was associated with less incidence of postinduction hypotension and vasopressor consumption in comparison to the 1:3 ratio with comparable intubation conditions. CLINICAL TRIAL REGISTRATION: NCT05166330. URL: https://clinicaltrials.gov/ct2/show/NCT05166330 .

Patient Selection in One Anastomosis/Mini Gastric Bypass-an Expert Modified Delphi Consensus.

PURPOSE: One anastomosis/mini gastric bypass (OAGB/MGB) is up to date the third most performed obesity and metabolic procedure worldwide, which recently has been endorsed by ASMBS. The main criticisms are the risk of bile reflux, esophageal cancer, and malnutrition. Although IFSO has recognized this procedure, guidance is needed regarding selection criteria. To give clinicians a daily support in performing the right patient selection in OAGB/MGB, the aim of this paper is to generate clinical guidelines based on an expert modified Delphi consensus. METHODS: A committee of 57 recognized bariatric surgeons from 24 countries created 69 statements. Modified Delphi consensus voting was performed in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was considered to indicate a consensus. RESULTS: Consensus was achieved for 56 statements. Remarkably, ≥ 90.0% of the experts felt that OAGB/MGB is an acceptable and suitable option "in patients with Body mass index (BMI) > 70, BMI > 60, BMI > 50 kg/m2 as a one-stage procedure," "as the second stage of a two-stage bariatric surgery after Sleeve Gastrectomy for BMI > 50 kg/m2 (instead of BPD/DS)," and "in patients with weight regain after restrictive procedures. No consensus was reached on the statement that OAGB/MGB is a suitable option in case of resistant Helicobacter pylori. This is likely as there is a concern that this procedure is associated with reflux and its related long-term complications including risk of cancer in the esophagus or stomach. Also no consensus reached on OAGB/MGB as conversional surgery in patients with GERD after restrictive procedures. Consensus for disagreement was predominantly achieved "in case of intestinal metaplasia of the stomach" (74.55%), "in patients with severe Gastro Esophageal Reflux Disease (GERD)(C,D)" (75.44%), "in patients with Barrett's metaplasia" (89.29%), and "in documented insulinoma" (89.47%). CONCLUSION: Patient selection in OAGB/MGB is still a point of discussion among experts. There was consensus that OAGB/MGB is a suitable option in elderly patients, patients with low BMI (30-35 kg/m2) with associated metabolic problems, and patients with BMIs more than 50 kg/m2 as one-stage procedure. OAGB/MGB can also be a safe procedure in vegetarian and vegan patients. Although OAGB/MGB can be a suitable procedure in patients with large hiatal hernia with concurrent hiatal hernia, it should not be offered to patients with grade C or D esophagitis or Barrett's metaplasia.

Outcomes of One Anastomosis Gastric Bypass in the IFSO Middle East North Africa (MENA) Region.

INTRODUCTION: Since it was first described in 2001, the one anastomosis gastric bypass (OAGB) has been gaining popularity in the Middle East region and worldwide. We designed a survey to evaluate the trends, techniques, and outcomes of OAGB in our region. METHODS: A questionnaire to study OAGB was sent to the members of the IFSO MENA chapter. RESULTS: One-hundred and forty-eight surgeons (74%) responded. Forty-six percent of all respondents (64 surgeons) performed OAGB routinely. The most commonly performed procedures were the laparoscopic sleeve gastrostomy (LSG), followed by OAGB, and then Roux-en-Y (RYGB). Of the surgeons who responded, 65% did not perform routine pre-operative endoscopy. Seventy-two percent believed that OAGB produces better weight loss than the LSG while 58% did not believe it produced better results to RYGB. The most common length of biliopancreatic limb utilized was 200 cm, and 72% of surgeons did not measure the total length of the small bowel. Fifty percent of the surgeons offered OAGB as a treatment for acid reflux and 33% offered it to active smokers. Early complications included leak (< 1%), venous thromboembolism (< 1%), and mortality (< 0.5%) in most centers. Leaks were managed conservatively (23%), by conversion to RYGB (20%), reinforcing the anastomosis (19%), reversal to normal anatomy (6%), and others (32%). Of the total surgeons, 41% reported revising at least one patient for malnutrition and steatorrhea, and 32% reported revising at least one patient for sever bile reflux. CONCLUSION: OAGB is a commonly performed and safe procedure in the MENA region. Malnutrition and bile reflux requiring surgical intervention are serious long-term concerns.

Incidence of and risk factors associated with pulmonary and extra-pulmonary tuberculosis in Saudi Arabia (2010-2011).

SETTING: National Tuberculosis Program, Department of Public Health, Ministry of Health, Kingdom of Saudi Arabia (KSA). OBJECTIVE: To summarize data on the incidence of tuberculosis and associated risk factors for cases reported during 2010-2011. DESIGN: Retrospective analysis of routinely collected data through an established national disease notification system of the Ministry of Health in KSA. RESULTS: The estimated incidence of all forms of tuberculosis fell from 15.8/100000 (95% CI: 15.3/100,000-16.3/100,000) in 2010 to 13.8/100,000 (95% CI: 13.4/100,000-14.2/100,000) in 2011. Saudis experienced a decrease from 11.8/100,000 (95% CI: 11.3/100,000 to 12.3/100,000) in 2010 to 9.9/100,000 (95% CI: 9.5/100,000-10.4/100,000) in 2011 while the incidence in non-Saudis declined from 24.7/100,000 (95% CI: 23.6/100,000 to 25.7/100,000) in 2010 to 22.5/100,000 (95% CI: 21.5/100,000 to 23.4/100,000) in 2011. The proportion of Extra Pulmonary TB (EPTB) which increased minimally from 30% in 2010 to 32% in 2011 was higher than global figures and strongly associated with age, sex, nationality and occupation. CONCLUSION: The current estimated incidence of about 14/100,000 in 2011 is less than half its estimated value of 44/100000 in 1990. Without prejudice to any under-reporting, the KSA appeared to be on the course for TB elimination by 2050 having reached the first milestone set by WHO. The proportion of EPTB remains higher than global figure and age, sex, nationality and occupation were significant independent predictors of EPTB.

Pinolide, a new nonenolide produced by Didymella pinodes , the causal agent of ascochyta blight on Pisum sativum.

An aggressive isolate of Didymella pinodes isolated from pea ( Pisum sativum ) produced four different metabolites in vitro. The metabolites isolated from the culture filtrates were characterized by spectroscopic and optical methods. A new nonenolide, named pinolide, was isolated and characterized as (2S*,7R*,8S*,5E,9R*)-2,7,8-trihydroxy-9-propyl-5-nonen-9-olide. Pinolidoxin, the main toxin produced by D. pinodes, was also isolated together with two other closely related nonenolides, identified as herbarumin II and 2-epi-herbarumin II. Herbarumin II and 2-epi-herbarumin II have been previously isolated from the fungi Phoma herbarum and Paraphaeosphaeria recurvifoliae , respectively, but described here to be isolated for the first time from D. pinodes. When tested on leaves of the host plant and other legumes and weeds, pinolidoxin was phytotoxic in all of the plant species, whereas the other three nonenolides did not produce any symptoms. The importance of the stereochemistry of the hydroxy group at C-7 on phytotoxicity also is discussed.

Ascosonchine, the enol tautomer of 4-pyridylpyruvic acid with herbicidal activity produced by Ascochyta sonchi.

A new phytotoxic enol tautomer of 4-pyridylpyruvic acid, named ascosonchine, was isolated from the culture filtrate of Ascochyta sonchi. Such a leaf pathogen is a potential biocontrol agent of Sonchus arvensis, a perennial herbaceous weed occurring throughout the temperate regions of the world. Ascosonchine, characterised as (Z)-2-hydroxy-3-(4-pyridyl)-2-propenoic acid by spectroscopic methods, showed selective herbicidal properties, that are not associated with antibacterial, antifungal or zootoxic activities.

Extension of the J-based configuration analysis to multiple conformer equilibria: an application to sapinofuranone A.

[structure: see text] A new strategy that extends the application of the J-based configuration analysis to systems characterized by multiple conformer equilibria is described and applied to sapinofuranone A (1), a phytotoxic molecule produced by three strains of Sphaeropsis sapinea. This method, based on a combination of computational techniques and NMR spectroscopy, uses ab initio calculations to predict a set of theoretical homo- and heteronuclear J values which can be compared against experimental NMR data.