BackgroundContamination of hospital surfaces by clinically-relevant pathogens represents a major concern in healthcare facilities, due to its impact on transmission of healthcare-associated infections (HAIs) and to the growing drug resistance of HAI-associated pathogens. Routinely used chemical disinfectants show limitations in controlling pathogen contamination, due to their inefficacy in preventing recontamination and selection of resistant strains. Recently we observed that an innovative approach, based on a cleanser added with spores of non-pathogenic probiotic Bacilli, was effective in stably counteracting the growth of several pathogens contaminating hospital surfaces.MethodsHere, we wanted to study the impact of the Bacillus-based cleanser on the drug-resistance features of the healthcare pathogens population. In parallel, the ability of cleanser-derived Bacilli to infect hospitalized patients was also investigated.ResultsCollected data showed that Bacilli spores can germinate on dry inanimate surfaces, generating the bacterial vegetative forms which counteract the growth of pathogens and effectively substitute for them on treated surfaces. Strikingly, this procedure did not select resistant species, but conversely induced an evident decrease of antibiotic resistance genes in the contaminating microbial population. Also importantly, all the six HAI-positive patients hosted in the treated areas resulted negative for probiotic Bacilli, thus adding evidences to their safety-to-use.ConclusionsThese results indicate that this probiotic-based procedure is active not only in controlling surface microbial contamination but also in lowering drug-resistant species, suggesting that it may have relevant clinical and therapeutical implications for the management of HAIs.

BackgroundHealthcare-Associated Infections (HAIs) are one of the most frequent complications occurring in healthcare facilities. Contaminated environmental surfaces provide an important potential source for transmission of many healthcare-associated pathogens, thus indicating the need for new and sustainable strategies.AimThis study aims to evaluate the effect of a novel cleaning procedure based on the mechanism of biocontrol, on the presence and survival of several microorganisms responsible for HAIs (i.e. coliforms, Staphyloccus aureus, Clostridium difficile, and Candida albicans) on hard surfaces in a hospital setting.MethodsThe effect of microbial cleaning, containing spores of food grade Bacillus subtilis, Bacillus pumilus and Bacillus megaterium, in comparison with conventional cleaning protocols, was evaluated for 24 weeks in three independent hospitals (one in Belgium and two in Italy) and approximately 20000 microbial surface samples were collected.ResultsMicrobial cleaning, as part of the daily cleaning protocol, resulted in a reduction of HAI-related pathogens by 50 to 89%. This effect was achieved after 3–4 weeks and the reduction in the pathogen load was stable over time. Moreover, by using microbial or conventional cleaning alternatively, we found that this effect was directly related to the new procedure, as indicated by the raise in CFU/m2 when microbial cleaning was replaced by the conventional procedure. Although many questions remain regarding the actual mechanisms involved, this study demonstrates that microbial cleaning is a more effective and sustainable alternative to chemical cleaning and non-specific disinfection in healthcare facilities.ConclusionsThis study indicates microbial cleaning as an effective strategy in continuously lowering the number of HAI-related microorganisms on surfaces. The first indications on the actual level of HAIs in the trial hospitals monitored on a continuous basis are very promising, and may pave the way for a novel and cost-effective strategy to counteract or (bio)control healthcare-associated pathogens.

Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.

Although mitochondria play a multifunctional role in cancer progression and Ca2+ signaling is remodeled in a wide variety of tumors, the underlying mechanisms that link mitochondrial Ca2+ homeostasis with malignant tumor formation and growth remain elusive. Here, we show that phosphorylation at the N‐terminal region of the mitochondrial calcium uniporter (MCU) regulatory subunit MICU1 leads to a notable increase in the basal mitochondrial Ca2+ levels. A pool of active Akt in the mitochondria is responsible for MICU1 phosphorylation, and mitochondrion‐targeted Akt strongly regulates the mitochondrial Ca2+ content. The Akt‐mediated phosphorylation impairs MICU1 processing and stability, culminating in reactive oxygen species (ROS) production and tumor progression. Thus, our data reveal the crucial role of the Akt‐MICU1 axis in cancer and underscore the strategic importance of the association between aberrant mitochondrial Ca2+ levels and tumor development.

Olivieri O. Activated factor VII-antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study.J Thromb Haemost 2016; 14: 655-66. Essentials• Activated factor VII-antithrombin complex (FVIIa-AT) in plasma may reflect tissue factor exposure.• FVIIa-AT levels were assessed in an angiographically controlled coronary artery disease (CAD) cohort.• High FVIIa-AT levels correlated with an increased thrombin generation.• High FVIIa-AT levels were associated with a greater risk of mortality in patients with stable CAD.Summary. Background: Plasma concentration of activated factor VII (FVIIa)-antithrombin (AT) complex has been proposed as an indicator of intravascular exposure of tissue factor. Objectives: The aims of this observational study were to evaluate (i) FVIIa-AT plasma concentration in subjects with or without coronary artery disease (CAD) and (ii) its association with mortality in a prospective cohort of patients with CAD. Methods: FVIIa-AT levels were measured by ELISA in 686 subjects with (n = 546) or without (n = 140) angiographically proven CAD. Subjects with acute coronary syndromes and those taking anticoagulant drugs at the time of enrollment were excluded. CAD patients were followed for total and cardiovascular mortality. Results: There was no difference in FVIIa-AT levels between CAD (84.8 with 95% confidence interval [CI] 80.6-88.2 pmol L -1 ) and CAD-free subjects (83.9 with 95% CI 76.7-92.8 pmol L -1 ). Within the CAD population, during a 64-month median followup, patients with FVIIa-AT levels higher than the median value at baseline (≥ 79 pmol L -1 ) had a two-fold greater risk of both total and cardiovascular mortality. Results were confirmed after adjustment for sex, age, the other predictors of mortality (hazard ratio for total mortality: 2.05 with 95% CI 1.22-3.45, hazard ratio for cardiovascular mortality 1.94 with 95% CI 1.01-3.73, with a slight improvement of C-statistic over traditional risk factors), FVIIa levels, drug therapy at discharge, and even patients using all the usual medications for CAD treatment. High FVIIa-AT levels also correlated with increased thrombin generation. Conclusions: This preliminary study suggests that plasma concentration of FVIIa-AT is a thrombophilic marker of total and cardiovascular mortality risk in patients with clinically stable CAD.