Search Results (45)

Being first applied for the treatment of infectious diseases of the gut at the start of the 20th century, bacteriophages are again now considered as alternative antimicrobial tools for targeting antibiotic-resistant enterobacteria. Here, we report the new bacteriophage Escherichia phage KEC4 isolated from the Kukshum River (Chuvash Republic, Russia), lysing Escherichia coli and belonging to the Septuagintavirus genus. The genome consists of 145,125 bp with a GC content of 41.3% and contains 6 tRNA and 303 protein-coding sequences. Among them, only 72 encode proteins with known functions, while no proteins potentially associated with lysogeny can be identified. The bacteriophage forms round and pure plaques 0.3–1 mm in diameter and is capable of lysing 14 of 31 E. coli clinical isolates with multiple resistance patterns. Furthermore, in the presence of KEC4, the MICs of meropenem and kanamycin decreased 16-fold in the reference strain. In clinical multidrug-resistant isolates, a 16-fold decrease in the MIC was observed for aminoglycosides (amikacin and gentamicin) for the isolate NKC1, and an eight-fold drop in the MIC of ceftriaxone was observed for isolate 167, with no increase in the efficiency of aminoglycosides. Finally, a four-fold increase in the efficiency of both azithromycin and gentamicin was detected in isolate 5767. Taken together, these data characterize the new Escherichia phage KEC4 as a promising tool for the treatment of infections associated with Escherichia coli, while a preliminary assessment of both the isolate specificity of the phage and an antimicrobial susceptibility test would be required for successful elimination of the pathogen. Full article

Bacteriophages are promising antibacterial agents for managing acne vulgaris caused by Cutibacterium acnes, particularly given increasing antibiotic resistance. Here, we isolated and characterized two lytic Cutibacterium phages, NS-ph1 and NS-ph2, from acne lesions. Both bacteriophages exhibited a broad lytic spectrum, with a high activity against 27 C. acnes strains. Adsorption assays indicated rapid attachment and one-step growth experiments revealed latent periods of 4 h (NS-ph1) and 2 h (NS-ph2) and burst sizes of 70 and 59 PFU per infected cell, respectively. After long-term storage at room temperature, both phages retained infectivity for 3 months. Genome sequencing revealed linear dsDNA genomes of 29,490 bp (NS-ph1) and 29,189 bp (NS-ph2) with 51 and 46 predicted ORFs, respectively, and no tRNAs. No genes associated with lysogeny, toxins, or antibiotic resistance were detected. Comparative genomics placed both phages within the genus Pahexavirus. Together, these data expand the diversity of Pahexavirus and provide two well-characterized lytic candidates for further evaluation in anti-acne phage therapy. Full article

Protected areas (PAs) constitute a fundamental strategy for mitigating biodiversity loss. The land–sparing approach has expanded in response to international agreements, but expansion of PAs does not guarantee conservation objectives. The objective was to assess PA effectiveness in conserving Nothofagus antarctica forests in Santa Cruz (Argentina), evaluating human impacts associated with fires, animal uses, and harvesting. The research was conducted within pure native forests in Santa Cruz, Argentina. This province encompasses 52 protected areas, representing the highest concentration of conservation units within the forested landscapes across Argentina. At least eight PAs included N. antarctica forests. Three land tenure categories were evaluated: protected areas (PAs), a buffer of 15 km from PA boundaries on private lands (BL), and private lands (PL) outside the buffer. In total, 103 stands were sampled, where 38 variables were assessed (impacts, soil, forest structure, understory, and animal use). Three indices were developed to analyze ecosystem integrity: forest structure (FI), soil (SI), and animal use (AI). PAs presented the highest FI (0.64 for PA, 0.44 for BL, and 0.30 for PL) and AI (0.60 for PA, 0.55 for BL, and 0.52 for PL), and together with buffer areas, the highest SI (0.43 for PA, 0.47 for BL, and 0.32 for PL). PAs were clearly distinct from private lands; however, sustained actions for livestock exclusion, harvest regulation, and fire management remain necessary for future sustainable planning at the landscape level. Full article

Bulleidia extructa strain PP_925, isolated from the periodontal pocket of a patient with periodontitis, is a Gram-positive Bacillota with an unusually compact genome of 1.38 Mb. Phylogenomic analyses place PP_925 within Erysipelotrichales and show close relatedness of Bulleidia to Solobacterium and Lactimicrobium, as well as the existence of previously undescribed related clades. The metabolic repertoire of PP_925 is strongly reduced: it retains glycolysis, the phosphotransacetylase–acetate kinase pathway, and arginine catabolism but lacks the tricarboxylic acid cycle and most de novo biosynthetic pathways for amino acids, nucleotides, fatty acids, cofactors, and vitamins, implying reliance on salvage and cross-feeding. Phylogenetic inference indicates independent peptidoglycan losses in multiple mycoplasma Erysipelotrichia-related lineages, while PP_925 has retained an ancestral Gram-positive cell wall despite extensive genomic reduction. The genome preserves systems crucial for host interaction and adaptability, including a horizontally acquired tad locus encoding type IV pili, a comG competence system, and several adherence-associated virulence factors. Defense mechanisms are diverse and include a CRISPR-Cas II-A system, a type II restriction–modification module adjacent to Gao_Qat-like genes, and the Wadjet system in a genome without prophages; CRISPR spacers indicate repeated encounters with Bacillota phages. Comparative genomics of PP_925 and related strains reveals a small core genome with lineage-specific adhesion and defense modules, indicating recent shared ancestry combined with adaptive flexibility under substantial genome reduction. Full article

Bacteriophages are powerful drivers of microbial evolution and are increasingly explored as alternatives to antibiotics against multidrug-resistant pathogens such as Pseudomonas aeruginosa. Here, we describe the isolation, phenotypic characterization and genomic, structural and evolutionary analysis of Pseudomonas phage Adele, a lytic myovirus representing a novel species within the genus Pakpunavirus (family Vandenendeviridae). Phage Adele exhibits a short latent period of 20 min, a burst size of 59 ± 11 virions per infected cell and a high virulence index, efficiently lysing non-O11 Pseudomonas aeruginosa strains and reducing biofilm biomass. In vivo, Adele confers marked protection in a Galleria mellonella infection model. Phylogenetic reconstruction, synteny analysis and structural modeling demonstrate the relatedness of Vandenendeviridae to phages of the Andersonviridae and Vequintavirinae clades, pointing to a stable, ancestral virion architecture that has undergone lineage-specific elaborations, including the duplication and divergence of tail tube proteins. The tail assembly chaperone gene employs a conserved −1 programmed ribosomal frameshift. Phage Adele encodes an elaborate set of metabolic reprogramming and anti-defense systems, reflecting extensive horizontal gene transfer. The combination of a conserved structural architecture and mosaic genome establishes Adele as an exemplary system for studying modular evolution in phages, alongside its demonstrated therapeutic efficacy. Full article

The world of laughter is often deemed frivolous. Clowns have taught us otherwise. This paper investigates the convoluted politics of laughter in relation to clowning, arguing that clowns (and the laughter they elicit) blur humour and horror and, in doing so, offer a corrective to officialdom. I analyse laughter as a social phenomenon (following Bergson, Benjamin, and Bakhtin) and as a mediating form, bound up in power structures and political concerns that are both local and transhistorical. To contextualise the (d)evolution of the clown, I first discuss ambiguity, misfitness, and failure, and then consider the English Clown Joseph Grimaldi and the French Pierrot Jean-Gaspard Deburau. These performers, I suggest, represent the two main strands of clowns in popular culture: the melancholy outcast and the murderous deviant. I explore each strand via 1920s silent films, including Sjöström’s He Who Gets Slapped (1924), Chaplin’s The Circus (1928), Leni’s The Man Who Laughs (1928), and Brenon’s Laugh, Clown, Laugh (1928). These are works of social indictment that debunk monolithic depictions of clowns and laughter, critiquing conformity, social asymmetries, vices, and industrial growth. Clowning is more than playing an artistic, sociocultural role: it hinges on radical resistance and carries a political valence. Full article

Background and Objectives: The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management. Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential biomarkers, using Chi-square tests and paired t-tests for analysis. As an exploratory analysis, staining intensity was also compared on clinical/demographic variables using linear and logistic regression. Results: There were 123 candidate biomarkers identified in 91 studies. Four candidate markers were selected for further investigation: aminopeptidase A (APA)/cluster of differentiation (CD)249, aminopeptidase N (APN)/CD13, gamma-glutamyl transferase (GGT), and neuron-specific enolase (NSE). APA, GGT, and APN all demonstrated reduced staining intensity in the tumor compared with normal tissue (p < 0.001 for all). NSE demonstrated a statistically significant increase in expression in tumor compared with normal tissue (p < 0.001), and this was more pronounced in patients aged >60 years (p = 0.038). Conclusions: The utility of APA, APN, and GGT as diagnostic biomarkers in clear cell RCC is limited. NSE may have some role as a biomarker for clear cell RCC, particularly among older patients; however, further investigation is required. Full article

Antibiotic-resistant Pseudomonas aeruginosa presents a critical global health challenge, particularly in hospital-acquired infections. Bacteriophages offer a promising therapeutic avenue due to their ability to target and lyse resistant strains. This study characterizes Pseudomonas phage Banzai, a newly isolated Pbunavirus (family Lindbergviridae) with lytic activity against multiple P. aeruginosa isolates, including multidrug-resistant strains. Genomic analysis revealed a 66,189 bp genome, lacking antibiotic resistance or virulence factors, and suggested a headful packaging mechanism and the presence of a bidirectional component in the replication. In vivo experiments using Galleria mellonella showed therapeutic potential, significantly improving larval survival (87% at 24 h). Host range analysis revealed activity against 13 of 30 P. aeruginosa isolates, including members of O1, O3, O5 and O6 in silico predicted serogroups. Phylogenomic analyses place phage Banzai within the genus Pbunavirus, sharing 94.8% intergenomic similarity with its closest relatives, supporting its classification as a novel species. These findings highlight phage Banzai as a potential candidate for phage therapy, demonstrating genomic stability, a strictly lytic lifestyle, and in vivo efficacy. Full article

Background: Colon capsule endoscopy (CCE) or panenteric capsule endoscopy (PCE) offers a promising, non-invasive diagnostic approach for patients with iron deficiency anaemia (IDA). However, high rates of conversion to conventional colonoscopy (CCC) following capsule procedures reduce cost-effectiveness and patient satisfaction. Optimising the faecal immunochemical test (FIT) threshold may improve patient stratification and reduce unnecessary conversions in future applications within the IDA diagnostic pathway. Methods: The CLEAR IDA study was a multicentre, retrospective observational study conducted across four UK hospitals. Data were collected over a six-month study period and included patients referred via the two-week-wait (2WW) cancer pathway for iron deficiency, with or without anaemia, over a 12-month timeframe. Colonoscopy findings were analysed and extrapolated using NHS England’s CCE-to-colonoscopy referral criteria to assess the predictive value of FIT for colorectal cancer (CRC), polyp burden, and CCC using ROC curve analysis. The optimal FIT threshold was identified through three complementary approaches: threshold-based analysis, decision curve analysis, and cost–benefit modelling. Results: A total of 1531 patients were analysed; only 1.6% underwent small bowel capsule endoscopy. The diagnostic accuracy (AUC) of FIT for predicting CRC, polypoidal lesions, and CCC was 0.78, 0.58, and 0.69, respectively. Threshold-based analysis identified FIT = 15 µg/g as the lowest level at which CCC rates significantly increased (p = 0.02; OR = 1.87; 95% CI: 1.07–3.14). Decision curve analysis showed a maximum net benefit at FIT = 17.6 µg/g, while cost–benefit modelling identified 9 µg/g as the most cost-effective. Raising the threshold to 10 µg/g resulted in a net loss of GBP –294.4 per patient. An optimal cost-effective FIT threshold range was identified between 10 and 17.6 µg/g. The threshold selection should be tailored to local service capacity and resource availability. Conclusions: While FIT alone is an imperfect triage tool, optimising thresholds between 10 and 17 µg/g may enhance cost-effectiveness and guide appropriate PCE use in IDA. Full article

The global transportation sector is rapidly shifting towards electrification, aiming to create more sustainable environments. As a result, there is a significant focus on optimizing performance and increasing the lifespan of batteries in electric vehicles (EVs). To achieve this, the battery pack must operate with constant current charging and discharging modes of operation. Further, in an EV powertrain, maintaining a constant DC link voltage at the input stage of the inverter is crucial for driving the motor load. To satisfy these two conditions simultaneously during the energy transfer, a hybrid energy storage system (HESS) consisting of a lithium–ion battery and a supercapacitor (SC) connected to the semi-active topology of the bidirectional DC–DC converter (SAT-BDC) in this research work. However, generating the duty cycle for the switches to regulate the operation of SAT-BDC is complex due to the simultaneous interaction of the two mentioned constraints: regulating the DC link voltage by tracking the reference and maintaining the battery current at a constant value. Therefore, this research aims to efficiently resolve the issue by incorporating a highly flexible nonlinear model predictive control (NMPC) to control the switches of SAT-BDC. Furthermore, the converter system design is tested for operational performance using MATLAB 2022B with the battery current and the DC link voltage with different priorities. In the NMPC approach, these constraints are carefully evaluated with varying prioritizations, representing a crucial trade-off in optimizing EV powertrain operation. The results demonstrate that battery current prioritization yields better performance than DC link voltage prioritization, extending the lifespan and efficiency of batteries. Thus, this research work further aligns with the conceptual realization of the sustainability goals by minimizing the environmental impact associated with battery production and disposal. Full article

The tropical dry regions in the Neotropics are under intense anthropogenic pressures, resulting in changes for local communities related with their life patterns, wellbeing, and their relationship with ecosystems. The region has a history of human occupation that has shaped the traditional use of resources. We evaluated the richness, redundancy, and divergence of traditional uses of tree species present in vegetation patches of the tropical dry region of the Gulf of Mexico using functional diversity indices. The most used species are Acacia cochliacantha, Cedrela odorata, Enterolobium cyclocarpum, Gliricidia sepium, and Guazuma ulmifolia, and the uses with the broadest distributions across the region are firewood and pasture management, while reforestation is the least common use. While distance to the nearest patch of the closest human settlement is the most predictive variable associated with inhabitants’ different uses or recognitions of the value of different plant species, the most recognized and valued species are widely distributed in Mexico. Even when the forest cover is greatly reduced, the inhabitants recognize numerous uses that can be obtained from the vegetation patches. The approach used in this work provides important baseline information, as well as a methodology that facilitates the identification of priority areas for conservation. Full article

There is a lack of rapid dietary assessment tools to screen for compliance with guidelines for cancer prevention, such as those issued by the World Cancer Research Fund and the American Institute for Cancer Research. Our aim was to develop and validate a short screener (Nutri S-Can) to evaluate adherence to these recommendations, with the potential to be used in cancer prevention strategies. Four stages were defined: development, pilot study, refinement and validation study. The Nutri S-Can captures several domains of the WCRF/AICR recommendations: body composition, physical activity, diet, alcohol consumption, and breastfeeding. A first version was piloted in n = 100 PREDIMED-Plus study participants, for which comprehensive dietary, physical activity, and anthropometric measurements were available (+/− 6 months). Nutri S-Can was retested 6 months later in a subsample of 60 participants. Its validity was evaluated by comparing total and individual domain scores of the screener to those obtained from validated methods (breastfeeding not validated), and its reproducibility was measured comparing the first to the second administration (Pearson correlation). The first version of the Nutri S-Can included 15 questions distributed across five domains. Each question had three possible answers to determine whether participants meet (1 point), partially meet (0.5) or do not meet (0) the recommendations (score range: 0–7). Participant’s average age was 71.4 ± 5.03 y (41 women, 59 men), taking an average of 6.9 min to complete the screener. The total average score was 4.9 ± 0.9 vs. 3.5 ± 0.9 using data from validated questionnaires (high correlation; r = 0.51). Individual domains presented a high and significant correlation (r = 0.25–0.85) when comparing Nutri S-Can to validated assessments, except for processed foods (r = 0.15). A high correlation (r > 0.3) was observed when comparing Nutri S-Can before and after 6 months for individual dimensions and overall score. The refinement study aimed to increase preciseness and accuracy: two additional questions were included (total: 17 questions) to reduce the under-estimation of processed foods and improve self-classification of physical activity, and the nº of answers available was increased to six. This final version is being validated in two different populations (university students (n = 100) and PREDIMED-Plus participants (n = 117)) with the aim of having a validated screener that can be used in clinical settings at the individual level. Full article

(1) Background: VR is based on a virtual world that creates sounds effects and videos that replace the real environment. Arising literature shows VR efficacy in the field of neurological rehabilitation (NR) and that its use is also taking a place in musculoskeletal rehabilitation (MSR), as a treatment of various disorders that cause disability and chronic pain. (2) Aim: We discuss the role of VR in MSR, presenting its use and development on acute and chronic musculoskeletal disorders, based on the most recent literature. (3) Design and Methods: Literature searches were conducted in the databases Pubmed and Medline up to 30 September 2023. The PRISMA-Scr Checklist was followed. (4) Results: A total of 51 records were included. The analysed studies were conducted within a variety of populations, musculoskeletal disorders, settings, and VR technologies. Only a few studies could statistically affirm the efficacy of VR in MSR, as mentioned for the rehabilitation of the upper limb. Nevertheless, the observed trend is an improvement of the global perceived effect compared to traditional rehabilitation. (5) Conclusion: VR allows for the personalisation of treatment with an adaptable treatment platform, which may improve the participation of the patient and increase acceptability and adherence to long-term rehabilitation programs. We provide recommendations and suggestions for future research and use of VR in musculoskeletal rehabilitation. Full article

Satellite-derived Ecosystem Functional Types (EFTs) are increasingly used in ecology and conservation to characterize ecosystem heterogeneity. The diversity of EFTs, also known as Ecosystem Functional Diversity (EFD), has been suggested both as a potential metric of ecosystem-level biodiversity and as a predictor for ecosystem functioning, ecosystem services, and resilience. However, the impact of key methodological choices on patterns of EFTs and EFD have not been formally assessed. Using Costa Rica as a study system, we compared EFTs and EFD, derived from MODIS and Landsat data using different methodological assumptions, at both national and local extents. Our results showed that the regional spatial patterns of EFTs and EFD derived from 250 m MODIS and 30 m Landsat are notably different. The selection of sensors for deriving EFTs and EFD is dependent on the study area, data quality, and the research objective. Given its finer spatial resolution, Landsat has greater capacity to differentiate more EFTs than MODIS, though MODIS could be a better choice in frequently cloudy areas due to its shorter revisiting time. We also found that the selection of spatial extent used to derive EFD is critical, as smaller extents (e.g., at a local rather than a national scale) can show much higher diversity. However, diversity levels derived at smaller extents appear to be nested within the diversity levels derived at larger extents. As EFTs and EFD continue to develop as a tool for ecosystem ecology, we highlight the important methodological choices to ensure that these metrics best fit research objectives. Full article