Effectiveness of cephalosporins in hydrolysis and inhibition of Staphylococcus aureus and Escherichia coli biofilms.

IMPORTANCE: Staphylococcus aureus and Escherichia coli contribute to global health challenges by forming biofilms, a key virulence element implicated in the pathogenesis of several infections. OBJECTIVE: The study examined the efficacy of various generations of cephalosporins against biofilms developed by pathogenic S. aureus and E. coli. METHODS: The development of biofilms by both bacteria was assessed using petri-plate and microplate methods. Biofilm hydrolysis and inhibition were tested using first to fourth generations of cephalosporins, and the effects were analyzed by crystal violet staining and phase contrast microscopy. RESULTS: Both bacterial strains exhibited well-developed biofilms in petri-plate and microplate assays. Cefradine (first generation) showed 76.78% hydrolysis of S. aureus biofilm, while significant hydrolysis (59.86%) of E. coli biofilm was observed by cefipime (fourth generation). Similarly, cefuroxime, cefadroxil, cefepime, and cefradine caused 78.8%, 71.63%, 70.63%, and 70.51% inhibition of the S. aureus biofilms, respectively. In the case of E. coli, maximum biofilm inhibition (66.47%) was again shown by cefepime. All generations of cephalosporins were more effective against S. aureus than E. coli, which was confirmed by phase contrast microscopy. CONCLUSIONS AND RELEVANCE: Cephalosporins exhibit dual capabilities of hydrolyzing and inhibiting S. aureus and E. coli biofilms. First-generation cephalosporins exhibited the highest inhibitory activity against S. aureus, while the third and fourth generations significantly inhibited E. coli biofilms. This study highlights the importance of tailored antibiotic strategies based on the biofilm characteristics of specific bacterial strains.

Enhanced surveillance of hospitalised COVID-19 patients in Europe: I-MOVE-COVID-19 surveillance network, February 2020 to December 2021.

BackgroundIn early 2020, the I-MOVE-COVID-19 hospital surveillance system was adapted from an existing influenza surveillance system to include hospitalised COVID-19 cases.AimTo describe trends in the demographic and clinical characteristics of hospitalised COVID-19 cases across Europe during the first 2 years of the pandemic, and to identify associations between sex, age and chronic conditions with admission to intensive care or high dependency units (ICU/HDU) and in-hospital mortality.MethodsWe pooled pseudonymised data from all hospitalised COVID-19 cases in 11 surveillance sites in nine European countries, collected between 1 February 2020 and 31 December 2021. Associations between sex, age and chronic conditions, with ICU/HDU admission and in-hospital mortality were examined using Pearson's chi-squared test, and crude odds ratio (OR) estimates with respective 95% confidence intervals (CI).ResultsOf 25,971 hospitalised COVID-19 cases, 55% were male, 35% were 75 years or older and 90% had a chronic underlying condition. Patients with two or more chronic underlying conditions were significantly more likely to die in-hospital from COVID-19 (OR: 10.84; 95% CI: 8.30-14.16) than those without a chronic condition.ConclusionThe surveillance demonstrated that males, those 75 years or older and those with chronic conditions were at greater risk of in-hospital death. Over the surveillance period, outcomes tended to improve, likely because of vaccinations. This surveillance has laid the groundwork for further research studies investigating the risk factors of hospitalised COVID-19 cases and vaccine effectiveness.

A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic ß Cells from Human Embryonic Stem Cells.

The transplantation of human embryonic stem cell (hESC)-derived insulin-producing ß cells for the treatment of diabetes is finally approaching the clinical stage. However, even with state-of-the-art differentiation protocols, a significant percentage of undefined non-endocrine cell types are still generated. Most importantly, there is the potential for carry-over of non-differentiated cell types that may produce teratomas. We sought to modify hESCs so that their differentiated progeny could be selectively devoid of tumorigenic cells and enriched for cells of the desired phenotype (in this case, ß cells). Here we report the generation of a modified hESC line harboring two suicide gene cassettes, whose expression results in cell death in the presence of specific pro-drugs. We show the efficacy of this system at enriching for ß cells and eliminating tumorigenic ones both in vitro and in vivo. Our approach is innovative inasmuch as it allows for the preservation of the desired cells while eliminating those with the potential to develop teratomas.

Antihypertensive, antidyslipidemic and endothelial modulating activities of Orchis mascula.

The objective of this study was to investigate the possible mode(s) of action for the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly (P<0.05) reduced systolic blood pressure to 174.2+/-9.63 vs. 203.4+/-7.13 mm Hg (mean+/-s.e.m.; n=7-10) and improved endothelial dysfunction by increasing acetylcholine-induced relaxation. In normotensive anesthetized rats, the crude extract of OM (Om.Cr) at 10 and 30 mg kg(-1) caused a dose-dependent attenuation of mean arterial pressure. OM also decreased serum triglycerides to 29.28+/-6.99 vs. 93.84+/-5.7 mg per 100 ml (P<0.001), low-density lipoprotein-cholesterol to 5.99+/-1.27 vs. 21.9+/-3.5 mg per 100 ml (P<0.05) and atherogenic index to 0.096+/-0.017 vs. 0.36+/-0.08 mg per 100 ml (P<0.05). OM significantly reduced lipid levels in tyloxapol and high fat diet-induced hyperlipidemia. In a second model, OM also reduced gain in body weight with a reduction in daily diet consumption. In isolated rabbit aorta, Om.Cr caused concentration-dependent relaxation of both phenylephrine and high K(+) (80 mM)-induced contractions and a rightward shift of the calcium concentration-response curves similar to the effect seen with verapamil. In conclusion, OM shows antihypertensive and endothelial-modulating effects mediated through multiple pathways that include direct vasodilation by calcium channel blockade and reduction of plasma lipids by inhibition of biosynthesis, absorption and secretion. This study rationalizes the medicinal use of OM in hypertension and dyslipidemia. However, further studies are required to identify the active constituents of this plant.