Search Results (31)

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii poses a critical threat due to its ability to acquire multiple resistance mechanisms and persist under antibiotic pressure. This study aimed to elucidate the molecular basis of imipenem resistance in clinical A. baumannii isolates by integrating phenotypic, molecular, transcriptional, and clonal analyses. Methods: Eleven A. baumannii isolates identified by MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were investigated. Antimicrobial susceptibility to imipenem and meropenem was assessed, followed by polymerase chain reaction (PCR) detection of Ade efflux pump, outer membrane porin, and OXA-type carbapenemase genes. Transcriptional responses to sub-inhibitory imipenem exposure were evaluated using quantitative real-time PCR, and clonal relatedness was assessed by arbitrarily primed PCR. Results: All isolates were carbapenem-resistant, with bla_OXA-23 detected in all isolates and bla_OXA-24 absent in one isolate. Transcriptional analysis revealed isolate-specific responses to imipenem exposure. Among Ade efflux pump components, only adeR exhibited expression changes, displaying either downregulation or upregulation depending on the isolate, whereas adeA, adeB, adeC, and adeS transcripts were not detected under the tested conditions. Outer membrane porin genes showed heterogeneous regulation, with ompA and carO downregulated, while some isolates showed increased expression. Expression of oprD varied among isolates, and omp33–36 transcripts were detected in a single isolate and were reduced after exposure. Clonal analysis identified nine distinct genotypes, indicating genetic diversity and the absence of clonal dominance. Conclusions: These findings highlight the multifactorial and heterogeneous nature of carbapenem resistance in A. baumannii, emphasizing the interplay between regulatory efflux mechanisms, porin modulation, and carbapenemase carriage. Full article

Acinetobacter baumannii is a leading intensive care unit (ICU) pathogen associated with high rates of carbapenem resistance and poor clinical outcomes. This narrative review synthesizes recent clinical, microbiological, and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding resistance mechanisms and therapeutic strategies. A literature review was performed in PubMed, Scopus, and Web of Science (January 2015–August 2025), focusing on multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, ICU-acquired infections, and pivotal trials involving cefiderocol and sulbactam–durlobactam. Resistance is driven by OXA-type carbapenemases (notably OXA-23/24/58), efflux systems (AdeABC/IJK/FGH), porin alterations (CarO, Omp33–36), and lipopolysaccharide (LPS) modifications conferring colistin resistance. Management options include polymyxins, optimized tigecycline dosing, β-lactam/β-lactamase inhibitors, and newer agents such as cefiderocol and sulbactam–durlobactam, though mortality and safety outcomes vary across trials. A comparative table is included, summarizing antimicrobial mechanism coverage, PK/PD parameters, and adverse effects to support regimen selection in ventilator-associated pneumonia (VAP) and bacteremia. Optimized, multimodal approaches integrating timely diagnostics, targeted combination therapies, infection prevention, and antimicrobial stewardship are essential to improve outcomes and limit the spread of MDR and XDR A. baumannii. Full article

Background: Given the increasing problem of antibiotic resistance in A. baumannii, this study examines in vitro how combinations of colistin, meropenem, and sulbactam influence the expression of genes associated with multiresistance in this pathogen. Methods: Three multidrug-resistant strains, isolated from clinical infections in Panama (2022–2023), were identified using Vitek 2 compact. Susceptibility by broth microdilution, qualitative synergy, time-kill curves, and gene expression analysis by quantitative PCR were performed. Results: Synergistic effects were observed for the colistin–meropenem combination in all three strains, while the sulbactam–colistin combination exhibit synergy only in one of the A. baumannii isolates. Time-kill assays revealed bactericidal effects for the colistin–meropenem and sulbactam–colistin combinations. qPCR analyses indicated that colistin, meropenem, and sulbactam modified the expression of the genes under study. Colistin–meropenem and meropenem–sulbactam combinations decreased the expression of blaADC and blaOXA-51, while sulbactam–colistin did not have a significant effect. carO expression levels were not reduced with any antibiotic combination, while adeB expression was reduced with all the combinations tested. omp33–36 expression varied depending on the antibiotic and strain. Conclusions: Therefore, this study offers a new perspective on how rational combinations of clinically used antibiotics have the potential to modulate gene expression and contribute to the control of MDR strains, indicating that high-dose combination therapy with sulbactam and colistin could offer improved efficacy in treating multidrug resistant Acinetobacter baumannii infections. Full article

The majority of the challenges faced in power system engineering are presented as constrained optimization functions, which are frequently characterized by their complicated architectures. Metaheuristics are mathematical techniques used to solve complicated optimization problems. One such technique, Artificial Rabbits Optimization (ARO), has been designed to address global optimization challenges. However, ARO has limitations in terms of search functionality, restricting its efficiency in dealing with constrained optimization environments. To improve ARO’s compatibility with a variety of challenging problems, this work proposes implementing the Cauchy mutation operator into the position-updating procedure during the exploration stage. Furthermore, a novel multi-mode control parameter is developed to facilitate a smooth transition between exploration and exploitation phases. The enhancements may boost the performance and serve as an effective optimization tool for tackling complex engineering tasks. The improved version is known as Cauchy Artificial Rabbits Optimization (CARO). The proposed CARO’s performance is evaluated using eleven power system challenges as part of the CEC2020 competition’s test set of real-world constrained problems. The experimental results demonstrate the practical applicability of the proposed CARO in engineering applications and provide areas for future investigation. Full article

This study aims to investigate the oxidative pyrolysis of biomass volatiles with a particular focus on the formation of liquid products. Furfural, hydroxyacetone, and 3,4-dimethoxybenzaldehyde were chosen as volatile model compounds. The impacts of the oxygen equivalence ratio (ER, 0–15%) and temperature (400–500 °C) on the product composition and distribution were examined using a two-stage quartz-tube reactor. The results showed that volatile pyrolysis was limited at the lower temperature of 400 °C even with oxygen introduction, while it could be significantly promoted at 500 °C as illustrated by the observed great decrease in the GC-MS peak areas of the volatile compounds especially under an oxidative atmosphere. For instance, the peak area of 3,4-dimethoxybenzaldehyde at 500 °C under an ER of 4% was only ~9% of that at 400 °C. Oxygen introduction enhanced the volatile decomposition with the formation of mainly permanent gases (although not given in the study) rather than liquid products, but distinct impacts were obtained for varied volatile compounds possibly due to their different chemical structures and autoignition temperatures. From the perspective of liquid product formation, furfural would undergo the cleavage of C-C/C-O bonds to form linear intermediates and subsequent aromatization to generate aromatics (benzene and benzofuran). The presence of oxygen could enhance the oxidative destruction of the C-C/C-O bonds and the removal of O from the molecules to form simple aromatics such as benzene, phenol, and toluene. Hydroxyacetone mainly underwent C-C/C-O cleavage that was further enhanced in the presence of oxygen; the resultant intermediates would recombine to generate acetoin and 2,3-pentanedione. A higher ER would directly oxidize the alcoholic hydroxyl group (-OH) into an aldehyde group (-CHO) to form methyl glyoxal, while 3,4-dimethoxybenzaldehyde mainly underwent cleavage and recombination of bonds connected with the benzene ring including aldehyde group (-CHO), C_Ar-O, C_Methoxy-O bonds, thus forming 1,2-dimethoxybenzene, toluene, and 3-hydroxybenzadehyde. This study provides more fundamental insights into the homogeneous oxidation of volatiles during the oxidative fast pyrolysis of biomass, facilitating the deployment of this technology. Full article

Nitrogen fertilization greatly affects the development of sugar beet leaf and photosynthetic activity. This study aimed to evaluate the dynamics of leaf SPAD index, chlorophyll a (Chl a), chlorophyll b (Chl b), carotenoids (Caro), and the macronutrient status (N, P, K, Na, Mg) in different N fertilization rates in sugar beet production. This study set up a two-year field experiment in Eastern Croatia. The N fertilization rate was applied as: N0—control, N1—only presowing fertilization (45 kg/ha), and N2—presowing with topdressing (99 kg/ha in 2014 and 85.5 kg/ha in 2015). In general, N fertilization has a significant (p ≤ 0.05) influence on leaf pigments, except for Chl b. With the highest N dose (N2), the Chl content in the leaves increased by 12% compared to the control treatment (0.75 mg/g FW). The Caro dynamics in the leaves of vegetative growth were significantly different (p ≤ 0.05); leaves in the younger growth stage at the end of May had the highest Caro content (0.011 mg/g FW). In general, the SPAD index was significantly different (p ≤ 0.05), among N fertilization, whereas the lowest SPAD was found at the control treatment (38.7) and the highest at the N2 treatment (40.8). In general, regarding nitrogen fertilization, the lowest SPAD readings had sugar beet leaves at the control treatment (38.7), whereas the highest was determined at the N2 treatment (40.8). A strong positive relationship (p ≤ 0.01) was determined for Chl a, Chl b, Chl a + b, and Chl a + b/Caro with the SPAD index, whereas an inverse relationship with the SPAD index was determined for Caro and Chl a/b. The results demonstrate that nitrogen application, particularly at higher rates, positively influences chlorophyll and carotenoid content, as well as overall plant health, which can inform agricultural practices for more sustainable and efficient sugar beet cultivation. Full article

The characterization of lignocellulosic biomass present in archaeological wood is crucial for understanding the degradation processes affecting wooden artifacts. The lignocellulosic fractions in both the external and internal parts of Moroccan archaeological cedar wood (9th, 12th, and 21st centuries) were characterized using infrared spectroscopy (FTIR-ATR deconvolution mode), X-ray diffraction (XRD), and SEM analysis. The XRD demonstrates a significant reduction in the crystallinity index of cellulose from recent to aging samples. This finding is corroborated by the FTIR analysis, which shows a significant reduction in the area profiles of the C-H crystalline cellulosic bands (1374, 1315, and 1265 cm⁻¹) and C-O-C (1150–1000 cm⁻¹). The alterations in the lignin fraction of aging samples (from the 9th and 12th centuries) were demonstrated by a reduction in the intensity of the bands at 1271 and 1232 cm⁻¹ (C_ar-O) and the formation of new compounds, such as quinones and/or diaryl carbonyl structures, within the 1700–1550 cm⁻¹ range. The SEM images of cedar wood samples from the 9th and 12th centuries reveal voids, indicating that the entire cell wall component has been removed, a characteristic feature of simultaneous white rot fungi. In addition, horizontal “scratches” were noted, indicating possible bacterial activity. Full article

Background/Objectives: A. baumannii is a prominent nosocomial pathogen due to its drug-resistant phenotype, representing a public health problem. In this study, the aim was to determine the effect of different antimicrobial combinations against selected multidrug-resistant (MDR) or extensive drug-resistant (XDR) isolates of A. baumannii. Methods: MDR or XDR A. baumannii isolates were characterized by assessing genes associated with drug resistance, efflux pumps, porin expression, and biofilm formation. The activities of antimicrobial combinations including tigecycline, ampicillin/sulbactam, meropenem, levofloxacin, and colistin were evaluated using checkerboard and time-to-kill assays on isolates with different susceptibility profiles and genetic characteristics. Results: Genetic characterization of MDR/XDR strains (n = 100) included analysis of OXA-24/40 gene carbapenemase (98%), genes encoding aminoglycoside-modifying enzymes (44%), and parC gene mutations (10%). AdeIJK, AdeABC, and AdeFGH efflux pumps were overexpressed in 17–34% of isolates. Omp33-36, OmpA, and CarO membrane porins were under-expressed in 50–76% of isolates; CarO was overexpressed in 22% of isolates. Isolates showed low biofilm production (11%). Synergistic activity was observed with levofloxacin-ampicillin/sulbactam and meropenem-colistin, which were able to inhibit bacterial growth. Conclusions: Genetic characteristics of A. baumannii were highly variable among the strains. Synergistic activity was observed with meropenem-colistin and levofloxacin-ampicillin/sulbactam combinations in the checkerboard method, but not in the time-to-kill assays. These discrepancies among both methods indicate that further studies are needed to determine the best therapeutic combination for treating infections by A. baumannii. Full article

This article examines the use of contemplation in the religious poetry of John Lydgate, a fifteenth-century Benedictine monk and poet from England. While our understanding of Lydgate as a Benedictine poet has gained scholarly momentum, his paraliturgical writings have received less sustained attention. In this article, I argue that Lydgate democratizes the millennium-old monastic practice of lectio and meditatio by introducing a new contemplative mode for lay- and non-Latinate people in the vernacular, which I refer to as a performative lectio domini. This lectio is on an image instead of scripture and takes place within the context of the liturgy. Lydgate offers directions for participation in a liturgical ritual, enabling his readers to fully inhabit the surplus of materiality, somatic movements, and figurative language emanating from the liturgy in order for them to abandon themselves to contemplation in the crux of the rite. By looking at the poem On Kissing at Verbum caro factum est as a case study, I demonstrate how for Lydgate the liturgical kiss becomes a threshold of encounter with Christ through the incarnation. Rather than producing an emotive response, as is often characterized, the liturgical kiss fosters an intellectual illumination and deeper knowledge of Christ crucified. Full article

The remote sensing ground-based platform for atmospheric research hosted by the ERATOSTHENES Centre of Excellence will be the key research infrastructure of the Cyprus Atmospheric Remote Sensing Observatory (CARO) in Limassol, Cyprus. Between the 27th of October to the 1st of November 2020, the lidar system observed a pronounced and well-aged stratospheric aerosol layer with a backscatter maximum around 10 km asl and clear wildfire smoke signatures. The observed smoke plume was caused by extreme wildfires on the west coast of the U.S. Long-range aerosol transport events observed over Limassol are used for the study of the influence of organic aerosol particles (serving as ice-nucleating particles, INPs) in a cirrus formation in the upper troposphere. Full article

Rosemary solid distillation waste (SWR), a by-product of the essential oil industry, represents an important source of phenolic antioxidants. Green technologies such as ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and accelerated solvent extraction (ASE) of phenolic compounds from SWR were optimized as valorization routes to maximize yield, rosmarinic acid (RMA), carnosol (CARO) and carnosic acid (CARA) contents. Response surface methodology was used in this context, with ethanol concentration (X₁), extraction temperature (X₂), and time (X₃) being the independent variables. A second-order polynomial model was fitted to the data, and multiple regression analysis and analysis of variance were used to determine model fitness and optimal conditions. Ethanol concentration was the most influential extraction parameter, affecting phenolic compounds, while the influence of other parameters was moderate. The optimized conditions were as follows: X₁: 67.4, 80.0, and 59.0%, X₂: 70, 51, and 125 °C, and X₃: 15, 10, and 7 min for MAE, UAE, and ASE, respectively. A comparison of optimized MAE, UAE, and ASE with conventional Soxhlet extraction techniques indicated that ASE provided a higher extraction yield and content of phenolic compounds. However, UAE represented the best process from an environmental point of view, allowing an improved extraction of phenolics from SWR with high energy efficiency and low energy costs. Full article

Pectobacterium carotovorum subsp. carotovorum (Pcc) is known to produce different types of bacteriocins, active protein substances that inhibit or kill related strains and are known to be induced by several factors. In this paper, we report the discovery, isolation, characterization, and functional analysis of Carocin S4, a novel low-molecular-weight bacteriocin (LMWB) from Pcc. A 2750 bp gene fragment was isolated from the chromosomal DNA of Pcc mutant strain rif-TO6, a rifampicin-resistant strain of TO6. The gene contains caroS4K and caroS4I within two open reading frames, which encode CaroS4K and CaroS4I, with molecular weights of about 90 kD and 10 kD, respectively. The unique characteristics of Carocin S4 were revealed after homology analysis with the previously discovered bacteriocins from Pcc. CaroS4K, which shares 23% and 85% homology with CaroS1K and CaroS3K, respectively, is also a deoxyribonuclease. However, unlike the two which can only hydrolyze genomic DNA, CaroS4K hydrolyzes both genomic and plasmid DNA. On the other hand, CaroS4K was found to be 90% homologous with CaroS2K but works differently in killing the target cell, as the latter is a ribonuclease. The optimal reaction temperature for CaroS4K to hydrolyze dsDNA is approximately 50 °C and requires the divalent metal ions Mg²⁺, Ca²⁺, and Zn²⁺ to catalyze its DNase activity. This study reveals another nuclease type of bacteriocin in Pcc, with CaroS4K and CaroS4I functioning as killer and immunity proteins, respectively. Full article

Infections caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 and prescribed for the treatment of CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported a higher-than-average all-cause mortality rate in patients treated with cefiderocol compared to the best available therapy. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population that is seemingly isogenic. Recent results have demonstrated that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here, we describe the molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were resistant to cefiderocol. To identify mutations and gene expression changes associated with cefiderocol heteroresistance, we subjected these variants to whole genome sequencing and global transcriptional analysis. We then assessed the impact of these mutations on the pharmacodynamic activity of cefiderocol via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses demonstrated significant modifications in levels of expression of genes associated with iron-uptake systems or β-lactam resistance. The bla_NDM-1 and bla_ADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes’ expression was reduced. One of the mutations common to both heteroresistant strains was mapped within ppiA, a gene associated with iron homeostasis in other species. Static time-kill assays demonstrated that supplementing cation-adjusted Mueller–Hinton broth with human serum albumin (HAS), the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. We conclude that exposing CRAB to fluids with high HSA concentrations facilitates the rise of heteroresistance associated with point mutations and transcriptional upregulation of genes coding for β-lactamases and biofilm formation. The findings from this study hold significant implications for understanding the emergence of CRAB resistance mechanisms against cefiderocol treatment. This understanding is vital for the development of treatment guidelines that can effectively address the challenges posed by CRAB infections. Full article

Background: Boron Neutron Capture Therapy (BNCT) is an emerging radiotherapy. There are ongoing efforts to develop a Canadian accelerator-based BNCT center. However, it remains unclear how Canadian radiation oncologists (RO), medical physicists (MP), and their trainees perceive BNCT and its impact on radiation oncology as a discipline. Methods: A survey was created to explore the knowledge of BNCT, its clinical role, and the support for Canadian research. It was distributed through the Canadian Association of Radiation Oncology (CARO) and the Canadian Organization of Medical Physicists (COMP). Results: We received 118 valid responses from all 10 provinces, from 70 RO (59.3%) and 48 MP (40.7%), including 9 residents. Most knew of BNCT and its indications (60.2%). Although many were unaware of the reasons behind early failures (44.1%), common reasons were a lack of clinical trials and an inaccessibility of neutron sources (42.4%) as well as reactor unsuitability (34.7%). Additionally, 90.6% showed definite (66.9%) or possible (23.7%) support for Canadian BNCT research, while 89% indicated a definite (56.8%) or possible (32.2%) willingness for BNCT referrals. Conclusions: Most ROs and MPs supported Canadian BNCT research and would refer patients. However, limited awareness and a lack of experiences remain a challenge. Educational sessions are needed to realize this innovative cancer treatment in Canada. Full article