Carbohydrates from Pseudomonas aeruginosa biofilms interact with immune C-type lectins and interfere with their receptor function

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with KDs in the nM range. These HMW carbohydrates contain 74.9–80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewisx, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reasons for Deafness and Hearing Loss

<p>For people who are mute or have trouble speaking, sign language, often known as hand speaking, has grown in popularity as a communication tool. Sign language is a language in which letters and words are expressed with hand gestures. Deaf and deaf-blind people have a difficult time understanding other people and their surroundings. Deaf people communicate with others through sign language in order to overcome their isolation. Those who are deaf-blind, on the other hand, are blind and rely on tactile sign language, which they interpret by touching the hands of others while making movements. People who are deaf or deaf-blind find it more difficult to interact with others in their community when they are unfamiliar with sign language or uncomfortable using the tactile form of it. Furthermore, as sign language is a form of communication with their surroundings, studying it is essential for deaf individuals as well as others who coexist with deaf individuals. The purpose of this robotic hand is to function as a communication tool for the deaf or deaf-blind individual using assistive technology. Furthermore, it can be a useful tool for deaf persons and those who wish to learn sign language to help with sign language instruction. <br> </p&gt

Advantages of Automated License Plate Recognition Technology

<p>Automatic Number Plate Recognition (ANPR) is a technology that can be utilized by mall and movie theater parking management as well as toll booths on roads, expressways, etc. to expedite the toll collection process. Automated systems to retain vehicle information are becoming more and more important as the number of vehicles rises. It is imperative that communication be prioritized in order to effectively manage traffic and reduce crime. Number plate recognition is a dependable technique for automatic vehicle identification. With current algorithms, which are based on the concept of learning, developing adequate outcomes takes a long time and a lot of experience. An innovative use of machine learning is Automatic Number Plate Detection, which recognizes photos and transforms them into text. Using picture segmentation, the system locates, picks up, and extracts the vehicle's image and number plate. Afterwards, optical character recognition technology is used to identify characters in the retrieved image. This technology is used in military zones, apartment buildings, and traffic surveillance. <br> </p&gt

Phytochemical Analysis, Analgesic and Anti-inflammatory Studies on the n-Hexane Soluble Fraction of Vernonia glaberrima

Vernonia species have been used in the management of pain and other ailments in traditional medicine. This study was aimed at investigating the phytochemical constituents, toxicity, analgesic and anti-inflammatory activities of the n-hexane soluble fraction of Vernonia glaberrima. Preliminary phytochemical screening of the n-hexane fraction revealed the presence of steroids and triterpenes while the intraperitoneal LD50 of the fraction using Lorke’s method was 2154 mg/kg indicating the fraction to be slightly toxic. The analgesic property of the fraction was assessed using acetic acid-induced writhing test in mice and formalin-induced pain in rats while the anti-inflammatory effect was evaluated using formalin test in rats. The results of the study showed that the n-hexane fraction at the highest dose (500 mg/kg) decreased writhing response with 89.55 % inhibition. The fraction also exhibited significant (P<0.05) analgesic effect at both phases in the formalin test; the n-hexane fraction (250 and 500 mg/kg) and the standard drug, pentazocine (10 mg/kg) were able to significantly inhibit both phase while the extract 150 mg/kg diminished the pain induced by formalin in the first phase only. There was significant inhibition of oedema induced by carrageenan at the 1st hour (150 mg/kg) and the 4th hour at the graded doses of the fraction and the standard drug, piroxicam (10 mg/kg). The findings of this research suggests that the n-hexane soluble fraction of V. glaberrima contains bioactive constituents with analgesic and anti-inflammatory effect and thus, validates the use of the plant in the management of pain and inflammation in traditional medicine

Analgesic and anti-inflammatory activities of the n-butanol fraction of Vernonia glaberrima

The n-butanol leaf fraction of Vernonia glaberrima was evaluated for its toxicity, analgesic and anti-inflammatory effects. The leaves of V. glaberrima were collected, identified and extracted with methanol using maceration method and the resulting crude methanol extract was then partitioned using different solvents of increasing polarity (hexane, chloroform, ethyl acetate and n-butanol respectively). Preliminary phytochemical screening was conducted on the n-butanol fraction (BF) using standard procedures. The median lethal dose (LD50) of the fraction was determined using Lorke’s method and the analgesic effect was evaluated using acetic acid-induced writhing test in mice, while the anti-inflammatory activity was assessed using carrageenan-induced paw oedema in rats. Secondary metabolites including saponins, tannins, alkaloids, glycosides and flavonoids were found in the fraction. The LD50 of the fraction was 2154 mg/kg indicating the fraction to be moderately toxic. The fraction at 150 mg/kg exhibited 77.6 % inhibition of writhes, higher than the standard drug, piroxicam (10 mg/kg) which had 53.7 % inhibition. The n-butanol fraction at 150 and 250 mg/kg significantly inhibited the carrageenan-induced paw oedema at the 2nd and 4th hour, respectively, while there was no significant inhibition at 500 mg/kg of the fraction. The standard drug was only able to inhibit oedema at the 1st hour. The results showed the n-butanol fraction of V. glaberrima to possess significant analgesic and anti-inflammatory activities thereby validating its traditional use in the treatment of pain and inflammation

Carbohydrates From Pseudomonas Aeruginosa Biofilms Interact With Immune C-Type Lectins and Interfere With Their Receptor Function

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; \u3e132,000 Da), with Ks in the nM range. These HMW carbohydrates contain 74.9-80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewis, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection

Carbohydrates from Pseudomonas aeruginosa biofilms interact with immune C-type lectins and interfere with their receptor function

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with KDs in the nM range. These HMW carbohydrates contain 74.9–80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewisx, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit