Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species

Abstract Background: The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections. Among them, Acinetobacter baumannii has emerged as the most common pathogenic species involved in hospital-acquired infections. One reason for this emergence may be its persistence in the hospital wards, in particular in the intensive care unit; this persistence could be partially explained by the capacity of these microorganisms to form biofilm. Therefore, our main objective was to study the prevalence of the two main types of biofilm formed by the most relevant Acinetobacter species, comparing biofilm formation between the different species. Findings: Biofilm formation at the air-liquid and solid-liquid interfaces was investigated in different Acinetobacter spp. and it appeared to be generally more important at 25°C than at 37°C. The biofilm formation at the solid-liquid interface by the members of the ACB-complex was at least 3 times higher than the other species (80-91% versus 5-24%). In addition, only the isolates belonging to this complex were able to form biofilm at the air-liquid interface; between 9% and 36% of the tested isolates formed this type of pellicle. Finally, within the ACB-complex, the biofilm formed at the air-liquid interface was almost 4 times higher for A. baumannii and Acinetobacter G13TU than for Acinetobacter G3 (36%, 27% & 9% respectively). Conclusions: Overall, this study has shown the capacity of the Acinetobacter spp to form two different types of biofilm: solid-liquid and air-liquid interfaces. This ability was generally higher at 25°C which might contribute to their persistence in the inanimate hospital environment. Our work has also demonstrated for the first time the ability of the members of the ACB-complex to form biofilm at the air-liquid interface, a feature that was not observed in other Acinetobacter species

Barriers, facilitators, and other factors associated with health behaviors in childhood, adolescent, and young adult cancer survivors: A systematic review

\ua9 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.Background: Healthy behaviors are paramount in preventing long-term adverse health outcomes in childhood, adolescent, and young adult (CAYA) cancer survivors. We systematically reviewed and synthesized existing literature on barriers, facilitators, and other factors associated with health behaviors in this population. Methods: MEDLINE and PsycInfo were searched for qualitative and quantitative studies including survivors aged 16–50 years at study, a cancer diagnosis ≤25 years and ≥2 years post diagnosis. Health behaviors included physical activity, smoking, diet, alcohol consumption, sun exposure, and a combination of these behaviors (defined as health behaviors in general). Results: Barriers, facilitators, and other factors reported in ≥2 two studies were considered relevant. Out of 4529 studies, 27 were included (n = 31,905 participants). Physical activity was the most frequently examined behavior (n = 12 studies), followed by smoking (n = 7), diet (n = 7), alcohol (n = 4), sun exposure (n = 4), and health behavior in general (n = 4). Relevant barriers to physical activity were fatigue, lack of motivation, time constraints, and current smoking. Relevant facilitators were perceived health benefits and motivation. Influence of the social environment and poor mental health were associated with more smoking, while increased energy was associated with less smoking. No relevant barriers and facilitators were identified for diet, alcohol consumption, and sun exposure. Barriers to healthy behavior in general were unmet information needs and time constraints whereas lifestyle advice, information, and discussions with a healthcare professional facilitated healthy behavior in general. Concerning other factors, women were more likely to be physically inactive, but less likely to drink alcohol and more likely to comply with sun protection recommendations than men. Higher education was associated with more physical activity, and lower education with more smoking. Conclusion: This knowledge can be used as a starting point to develop health behavior interventions, inform lifestyle coaches, and increase awareness among healthcare providers regarding which survivors are most at risk of unhealthy behaviors

Anthropometry‐based prediction of body composition in early infancy compared to air‐displacement plethysmography

Funder: Danone Nutricia ResearchFunder: EU Commission for JPI HDHL program ‘Call III Biomarkers’ for project: BioFN ‐ Biomarkers for Infant Fat Mass Development and Nutrition; Grant(s): 696295Summary: Background: Anthropometry‐based equations are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air‐displacement plethysmography (ADP‐PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter‐1988, Aris‐2013, Catalano‐1995). Methods: Cambridge Baby Growth Study (CBGS), UK, had anthropometry data at 6 weeks (N = 55) and 3 months (N = 64), including skinfold thicknesses (SFT) at four sites (triceps, subscapular, quadriceps and flank) and ADP‐derived total body fat mass (FM) and fat‐free mass (FFM). Prediction equations for FM and FFM were developed in CBGS using linear regression models and were validated in Sophia Pluto cohort, the Netherlands, (N = 571 and N = 447 aged 3 and 6 months, respectively) using Bland–Altman analyses to assess bias and 95% limits of agreement (LOA). Results: CBGS equations consisted of sex, age, weight, length and SFT from three sites and explained 65% of the variance in FM and 79% in FFM. In Sophia Pluto, these equations showed smaller mean bias than the three published equations in estimating FM: mean bias (LOA) 0.008 (−0.489, 0.505) kg at 3 months and 0.084 (−0.545, 0.713) kg at 6 months. Mean bias in estimating FFM was 0.099 (−0.394, 0.592) kg at 3 months and −0.021 (−0.663, 0.621) kg at 6 months. Conclusions: CBGS prediction equations for infant FM and FFM showed better validity in an independent cohort at ages 3 and 6 months than existing equations

Comparison of the Virulence Potential of Acinetobacter Strains from Clinical and Environmental Sources

Several Acinetobacter strains have utility for biotechnology applications, yet some are opportunistic pathogens. We compared strains of seven Acinetobacter species (baumannii, Ab; calcoaceticus, Ac; guillouiae, Ag; haemolyticus, Ah; lwoffii, Al; junii, Aj; and venetianus, Av-RAG-1) for their potential virulence attributes, including proliferation in mammalian cell conditions, haemolytic/cytolytic activity, ability to elicit inflammatory signals, and antibiotic susceptibility. Only Ah grew at 102 and 104 bacteria/well in mammalian cell culture medium at 37°C. However, co-culture with colonic epithelial cells (HT29) improved growth of all bacterial strains, except Av-RAG-1. Cytotoxicity of Ab and Ah toward HT29 was at least double that of other test bacteria. These effects included bacterial adherence, loss of metabolism, substrate detachment, and cytolysis. Only Ab and Ah exhibited resistance to killing by macrophage-like J774A.1 cells. Haemolytic activity of Ah and Av-RAG-1 was strong, but undetectable for other strains. When killed with an antibiotic, Ab, Ah, Aj and Av-RAG-1 induced 3 to 9-fold elevated HT29 interleukin (IL)-8 levels. However, none of the strains altered levels of J774A.1 pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor-α). Antibiotic susceptibility profiling showed that Ab, Ag and Aj were viable at low concentrations of some antibiotics. All strains were positive for virulence factor genes ompA and epsA, and negative for mutations in gyrA and parC genes that convey fluoroquinolone resistance. The data demonstrate that Av-RAG-1, Ag and Al lack some potentially harmful characteristics compared to other Acinetobacter strains tested, but the biotechnology candidate Av-RAG-1 should be scrutinized further prior to widespread use

Antimicrobial activity of Ti-ZrN/Ag coatings for use in biomaterial applications

Severely broken bones often require external bone fixation pins to provide support but they can become infected. In order to reduce such infections, novel solutions are required. Titanium zirconium nitride (Ti-ZrN) and Ti-ZrN silver (Ti-ZrN/Ag) coatings were deposited onto stainless steel. Surface microtopography demonstrated that on the silver containing surfaces, Sa and Sv values demonstrated similar trends whilst the Ra, average height and RMS value and Sp values increased with increasing silver concentration. On the Ti-ZrN/Ag coatings, surface hydrophobicity followed the same trend as the Sa and Sv values. An increase in dead Staphylococcus aureus and Staphylococcus epidermidis cells was observed on the coatings with a higher silver concentration. Using CTC staining, a significant increase in S. aureus respiration on the silver containing surfaces was observed in comparison to the stainless steel control whilst against S. epidermidis, no significant difference in viable cells was observed across the surfaces. Cytotoxicity testing revealed that the TiZrN coatings, both with and without varying silver concentrations, did not possess a detrimental effect to a human monocyte cell line U937. This work demonstrated that such coatings have the potential to reduce the viability of bacteria that result in pin tract infections

Hexamerization-enhanced CD37 and CD20 antibodies synergize in CDC to kill patient-derived CLL cells with unprecedented potency

Transplantation and autoimmunit

Potent preclinical activity of HexaBody-DR5/DR5 in relapsed and/or refractory multiple myeloma

Apoptosis induction by death receptor (DR)-specific agonistic antibodies is a potentially effective antitumor therapy. Nonetheless, to date, all conventional DR-targeting antibodies that induce apoptosis via FcgR-dependent DR clustering failed to show clinical efficacy. HexaBody-DR5/DR5 (GEN1029) has been developed to overcome full FcgR dependence. HexaBody-DR5/DR5 is a mixture of 2 noncompeting DR5-specific immunoglobulin G1 (IgG1) antibodies, each with an E430G mutation in the Fc domain. This mutation enhances Fc-Fc interactions, resulting in antibody hexamerization, followed by FcgR-independent clustering of DR5 molecules. This unique combination of dual epitope targeting and increased IgG hexamerization resulted in potent preclinical antitumor activity in various solid cancers. In this study, we explored the preclinical activity of HexaBody-DR5/DR5 in multiple myeloma (MM), because MM cells are known to express DR5. In bone marrow samples from 48 MM patients, HexaBody-DR5/DR5 induced potent cytotoxicity of primary MM cells. Importantly, HexaBody-DR5/DR5 mediated the highest cytotoxic activity in samples from relapsed/refractory MM patients, including those who are refractory to daratumumab. This improved cytotoxic activity was observed only in patients who received their last anti-MM treatment,1 month ago, suggesting that anti-MM drugs sensitized MM cells to HexaBody-DR5/DR5. Supporting this, bortezomib combined with HexaBody-DR5/DR5 synergistically increased cytotoxicity in MM cells in 7 of 11 newly diagnosed patients. Lenalidomide also synergized with HexaBody-DR5/DR5, but only via its immunomodulatory effects, presumably by enhancing the antibody-dependent cellular cytotoxicity activity of HexaBody-DR5/DR5. Daratumumab showed additive effects when combined with HexaBody-DR5/DR5. In conclusion, the results of this preclinical study indicate a therapeutic potential for HexaBody-DR5/DR5, especially in recently treated relapsed/refractory MM patients

C1q potentiates DR5 agonist activity by a mixture of two DR5-specific HexaBody molecules

Transplantation and autoimmunit